Abstract
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been demonstrated to be a valuable tool to investigate noncovalent interactions of biomolecules. The direct detection of noncovalent assemblies is often more troublesome than with electrospray ionization. Using dedicated sample preparation techniques and carefully optimized instrumental parameters, a number of biomolecule assemblies were successfully analyzed. For complexes dissociating under MALDI conditions, covalent stabilization with chemical cross-linking is a suitable alternative. Indirect methods allow the detection of noncovalent assemblies by monitoring the fading of binding partners or altered H/D exchange patterns.
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Abbreviations
- ACN:
-
Acetonitrile
- ADP:
-
Adenosine-5′-diphosphate
- AMNP:
-
2-Amino-4-methyl-5-nitropyridine
- AMP:
-
Adenosine-5′-monophosphate
- ANA:
-
2-Aminonicotinic acid
- AP:
-
Atmospheric pressure
- ATP:
-
Adenosine-5′-triphosphate
- ATT:
-
6-Aza-2-thiothymine
- CHCA:
-
α-Cyano-4-hydroxycinnamic acid
- DHAP:
-
Dihydroxyacetophenone
- DHB:
-
Dihydroxybenzoic acid
- DNA:
-
Deoxyribonucleic acid
- ESI:
-
Electrospray ionization
- FA:
-
Ferulic acid
- hERα LBD:
-
Human estrogen receptor α ligand binding domain
- HIV:
-
Human immunodeficiency virus
- HPA:
-
3-Hydroxypicolinic acid
- IR:
-
Infrared
- iTRAQ:
-
Isobaric tag for relative and absolute quantitation
- K a :
-
Association constant
- K d :
-
Dissociation constant
- LILBID:
-
Laser induced liquid beam or bead ionization/desorption
- MALDI:
-
Matrix-assisted laser desorption/ionization
- MCP:
-
Microchannel plate detector
- MS:
-
Mass spectrometry
- NHS:
-
N-Hydroxysuccinimide
- PNA:
-
p-Nitroaniline
- RNA:
-
Ribonucleic acid
- SA:
-
Sinapinic acid
- TFA:
-
Trifluoroacetic acid
- THAP:
-
Trihydroxyacetophenone
- THF:
-
Tetrahydrofuran
- ToF:
-
Time-of-flight
- TrpR:
-
Tryptophan repressor
- UV:
-
Ultraviolet
References
Coux O, Tanaka K, Goldberg AL (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65:801–847
Davies DR, Padlan EA, Sheriff S (1990) Antibody-antigen complexes. Annu Rev Biochem 59:439–473
Scheeff ED, Bourne PE (2005) Structural evolution of the protein kinase-like superfamily. PLoS Comput Biol 1:e49
Terwilliger NB (1998) Functional adaptations of oxygen-transport proteins. J Exp Biol 201:1085–1098
McGhee JD, Felsenfeld G (1980) Nucleosome structure. Annu Rev Biochem 49:1115–1156
Thuong NT, Helene C (1993) Sequence-specific recognition and modification of double-helical DNA by oligonucleotides. Angew Chem Int Ed 32:666–690
Phizicky EM, Fields S (1995) Protein-protein interactions - methods for detection and analysis. Microbiol Rev 59:94–123
Wyttenbach T, Bowers MT (2007) Annu Rev Phys Chem 58:511–533
Bolbach G (2005) Matrix-assisted laser desorption/ionization analysis of non-covalent complexes: fundamentals and applications. Curr Pharm Des 11:2535–2557
Bich C, Zenobi R (2009) Mass spectrometry of large complexes. Curr Opin Struct Biol 19:632–639
Heck AJ (2008) Native mass spectrometry: a bridge between interactomics and structural biology. Nat Methods 5:927–933
Schalley CA (2001) Molecular recognition and supramolecular chemistry in the gas phase. Mass Spectrom Rev 20:253–309
Hardouin J, Hubert-Roux M, Delmas AF et al (2006) Identification of isoenzymes using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 20:725–732
Schermann SM, Simmons DA, Konermann L (2005) Mass spectrometry-based approaches to protein-ligand interactions. Expert Rev Proteomics 2:475–485
Rosinke B, Strupat K, Hillenkamp F et al (1995) Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of membrane-proteins and non-covalent complexes. J Mass Spectrom 30:1462–1468
Farmer TB, Caprioli RM (1991) Assessing the multimeric states of proteins: studies using laser desorption mass spectrometry. Biol Mass Spectrom 20:796–800
Wenzel RJ, Matter U, Schultheis L et al (2005) Analysis of megadalton ions using cryodetection MALDI time-of-flight mass spectrometry. Anal Chem 77:4329–4337
Twerenbold D, Gerber D, Gritti D et al (2001) Single molecule detector for mass spectrometry with mass independent detection efficiency. Proteomics 1:66–69
Frank M, Labov SE, Westmacott G et al (1999) Energy-sensitive cryogenic detectors for high-mass biomolecule mass spectrometry. Mass Spectrom Rev 18:155–186
Hillenkamp F, Nazabal A, Roehling U, Wenzel R (2008) Method for analyzing ions of high mass in time-of-flight mass spectrometer, involves applying potential difference between front and back sides of electron multiplier to multiply number of electrons. WO2009086642-A1 WOCH000007
Spengler B, Kirsch D, Kaufmann R et al (1990) The detection of large molecules in matrix-assisted UV-laser desorption. Rapid Commun Mass Spectrom 4:301–305
Chan TWD, Colburn AW, Derrick PJ (1992) Matrix-assisted laser desorption/ionization using a liquid matrix: formation of high-mass cluster ions from proteins. Oms 27:53–56
Juhasz P, Biemann K (1994) Mass spectrometric molecular-weight determination of highly acidic compounds of biological significance via their complexes with basic polypeptides. Proc Natl Acad Sci USA 91:4333–4337
Tang X, Callahan JH, Zhou P et al (1995) Noncovalent protein-oligonucleotide interactions monitored by matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem 67:4542–4548
Song F (2007) A study of noncovalent protein complexes by matrix-assisted laser desorption/ionization. J Am Soc Mass Spectrom 18:1286–1290
Benesch JLP, Ruotolo BT, Simmons DA et al (2007) Protein complexes in the gas phase: technology for structural genomics and proteomics. Chem Rev 107:3544–3567
Ruotolo BT, Giles K, Campuzano I et al (2005) Evidence for macromolecular protein rings in the absence of bulk water. Science 310:1658–1661
Karas M, Bahr U, Ingendoh A et al (1990) Principles and applications of matrix-assisted UV-laser desorption/ionization mass spectrometry. Anal Chim Acta 241:175–185
Karas M, Bahr U (1990) Laser desorption ionization mass spectrometry of large biomolecules. Trends Anal Chem 9:321–325
Hillenkamp F, Karas M, Beavis RC et al (1991) Matrix-assisted laser desorption/ionization mass spectrometry of biopolymers. Anal Chem 63:A1193–A1202
Zehl M, Allmaier G (2005) Instrumental parameters in the MALDI-TOF mass spectrometric analysis of quaternary protein structures. Anal Chem 77:103–110
Moniatte M, van der Goot FG, Buckley JT et al (1996) Characterisation of the heptameric pore-forming complex of the Aeromonas toxin aerolysin using MALDI-TOF mass spectrometry. FEBS Lett 384:269–272
Kirpekar F, Berkenkamp S, Hillenkamp F (1999) Detection of double-stranded DNA by IR- and UV-MALDI mass spectrometry. Anal Chem 71:2334–2339
Zehl M, Allmaier G (2004) Ultraviolet matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of intact hemoglobin complex from whole human blood. Rapid Commun Mass Spectrom 18:1932–1938
Von Seggern CE, Cotter RJ (2003) Fragmentation studies of noncovalent sugar-sugar complexes by infrared atmospheric pressure MALDI. J Am Soc Mass Spectrom 14:1158–1165
Von Seggern CE, Cotter RJ (2004) Study of peptide-sugar non-covalent complexes by infrared atmospheric pressure matrix-assisted laser desorption/ionization. J Mass Spectrom 39:736–742
Moyer SC, Marzilli LA, Woods AS et al (2003) Atmospheric pressure matrix-assisted laser desorption/ionization (AP MALDI) on a quadrupole ion trap mass spectrometer. Int J Mass Spectrom 226:133–150
Cohen LRH, Strupat K, Hillenkamp F (1997) Analysis of quaternary protein ensembles by matrix assisted laser desorption/ionization mass spectrometry. J Am Soc Mass Spectrom 8:1046–1052
Horneffer V, Strupat K, Hillenkamp F (2006) Localization of noncovalent complexes in MALDI-preparations by CLSM. J Am Soc Mass Spectrom 17:1599–1604
Wortmann A, Pimenova T, Alves S et al (2007) Investigation of the first shot phenomenon in MALDI mass spectrometry of protein complexes. Analyst 132:199–207
Gruic-Sovulj I, Lüdemann H-C, Hillenkamp F et al (1997) Detection of noncovalent tRNA-aminoacyl-tRNA synthetase complexes by matrix-assisted laser desorption/ionization mass spectrometry. J Biol Chem 272:32084–32091
Moniatte M, Lesieur C, Vécsey-Semjén B et al (1997) Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry in the subunit stoichiometry study of high-mass non-covalent complexes. Int J Mass Spectrom Ion Process 169(170):179–199
Vogl T, Roth J, Sorg C et al (1999) Calcium-induced noncovalently linked tetramers of MRP8 and MRP14 detected by ultraviolet matrix-assisted laser desorption/ionization mass spectrometry. J Am Soc Mass Spectrom 10:1124–1130
Strupat K, Sagi D, Bönisch H et al (2000) Oligomerization and substrate binding studies of the adenylate kinase from Sulfolobus acidocaldarius by matrix-assisted laser desorption/ionization mass spectrometry. Analyst 125:563–567
Jespersen S, Niessen WMA, Tjaden UR et al (1998) Basic matrices in the analysis of non-covalent complexes by matrix-assisted laser desorption/ionization mass spectrometry. J Mass Spectrom 33:1088–1093
Brunelle A, Chaurand P, Della-Negra S et al (1993) Surface secondary electron and secondary ion emission induced by large molecular ion impacts. Int J Mass Spectrom Ion Process 126:65–73
Coeck S, Beck M, Delaure B et al (2006) Microchannel plate response to high-intensity ion bunches. Nucl Instrum Meth A 557:516–522
Clark CG Jr, Wenzel RJ, Andreitchenko EV et al (2007) Controlled MegaDalton assembly with locally stiff but globally flexible polyphenylene dendrimers. J Am Chem Soc 129:3292–3301
Nazabal A, Wenzel R, Zenobi R (2006) Immunoassays with direct mass spectrometric detection. Anal Chem 78:3562–3570
Seyfried BK, Siekmann J, Belgacem O et al (2010) MALDI linear TOF mass spectrometry of PEGylated (glyco)proteins. J Mass Spectrom 45:612–617
van Remoortere A, van Zeijl RJM, van den Oever N et al (2010) MALDI imaging and profiling MS of higher mass proteins from tissue. J Am Soc Mass Spectrom 21:1922–1929
Kleinekofort W, Avdiev J, Brutschy B (1996) A new method of laser desorption mass spectrometry for the study of biological macromolecules. Int J Mass Spectrom Ion Process 152:135–142
Wattenberg A, Sobott F, Brutschy B (2000) Detection of intact hemoglobin from aqueous solution with laser desorption mass spectrometry. Rapid Commun Mass Spectrom 14:859–861
Wattenberg A, Sobott F, Barth HD et al (2000) Studying noncovalent protein complexes in aqueous solution with laser desorption mass spectrometry. Int J Mass Spectrom 203:49–57
Morgner N, Barth HD, Brutschy B (2006) A new way to detect noncovalently bonded complexes of biomolecules from liquid micro-droplets by laser mass spectrometry. Aust J Chem 59:109–114
Hoffmann J, Schmidt TL, Heckel A et al (2009) Probing the limits of liquid droplet laser desorption mass spectrometry in the analysis of oligonucleotides and nucleic acids. Rapid Commun Mass Spectrom 23:2176–2180
Morgner N, Barth HD, Brutschy B et al (2008) Binding sites of the viral RNA element TAR and of TAR mutants for various peptide ligands, probed with LILBID: a new laser mass spectrometry. J Am Soc Mass Spectrom 19:1600–1611
Morgner N, Kleinschroth T, Barth HD et al (2007) A novel approach to analyze membrane proteins by laser mass spectrometry: from protein subunits to the integral complex. J Am Soc Mass Spectrom 18:1429–1438
Morgner N, Zickermann V, Kerscher S et al (2008) Subunit mass fingerprinting of mitochondrial complex I. Biochim Biophys Acta Bioenerg 1777:1384–1391
Morgner N, Hoffmann J, Barth HD et al (2008) LILBID-mass spectrometry applied to the mass analysis of RNA polymerase II and an F1Fo-ATP synthase. Int J Mass Spectrom 277:309–313
Hoffmann J, Sokolova L, Preiss L et al (2010) ATP synthases: cellular nanomotors characterized by LILBID mass spectrometry. Phys Chem Chem Phys 12:13375–13382
Woods AS, Buchsbaum JC, Worrall TA et al (1995) Matrix-assisted laser desorption/ionization of noncovalently bound compounds. Anal Chem 67:4462–4465
Reichenbecher W, Rüdiger A, Kroneck PMH et al (1996) One molecule of molybdopterin guanine dinucleotide is associated with each subunit of the heterodimeric Mo-Fe-S protein transhydroxylase of Pelobacter acidigallici as determined by SDS/PAGE and mass spectrometry. Eur J Biochem 237:406–413
Salih B, Masselon C, Zenobi R (1998) Matrix-assisted laser desorption/ionization mass spectrometry of noncovalent protein-transition metal ion complexes. J Mass Spectrom 33:994–1002
Lehmann E, Zenobi R (1998) Detection of specific noncovalent zinc finger peptide-oligodeoxynucleotide complexes by matrix-assisted laser desorption/ionization mass spectrometry. Angew Chem Int Ed 37:3430–3432
Lehmann E, Zenobi R, Vetter S (1999) Matrix-assisted laser desorption/ionization mass spectra reflect solution-phase zinc finger peptide complexation. J Am Soc Mass Spectrom 10:27–34
Woods AS, Koomen JM, Ruotolo BT et al (2002) A study of peptide-peptide interactions using MALDI ion mobility o-TOF and ESI mass spectrometry. J Am Soc Mass Spectrom 13:166–169
Terrier P, Tortajada J, Zin G et al (2007) Noncovalent complexes between DNA and basic polypeptides or polyamines by MALDI-TOF. J Am Soc Mass Spectrom 18:1977–1989
Glocker MO, Bauer SHJ, Kast J et al (1996) Characterization of specific noncovalent protein complexes by UV matrix-assisted laser desorption ionization mass spectrometry. J Mass Spectrom 31:1221–1227
Lecchi P, Pannell LK (1995) The detection of intact double-stranded DNA by MALDI. J Am Soc Mass Spectrom 6:972–975
Lin S, Cotter RJ, Woods AS (1998) Detection of non-covalent interaction of single and double stranded DNA with peptides by MALDI-TOF. Protein Struct Funct Genet Suppl 2:12–21
Ohara K, Smietana M, Vasseur JJ (2006) Characterization of specific noncovalent complexes between guanidinium derivatives and single-stranded DNA by MALDI. J Am Soc Mass Spectrom 17:283–291
Lin S, Long S, Ramirez SM et al (2000) Characterization of the "helix clamp" motif of HIV-1 reverse transcriptase using MALDI-TOF MS and surface plasmon resonance. Anal Chem 72:2635–2640
Bahr U, Aygün H, Karas M (2008) Detection and relative quantification of siRNA double strands by MALDI mass spectrometry. Anal Chem 80:6280–6285
Sudha R, Zenobi R (2002) The detection and stability of DNA duplexes probed by MALDI mass spectrometry. Helv Chim Acta 85:3136–3143
Distler AM, Allison J (2002) Additives for the stabilization of double-stranded DNA in UV-MALDI MS. J Am Soc Mass Spectrom 13:1129–1137
Luo SZ, Li YM, Qiang W et al (2004) Detection of specific noncovalent interaction of peptide with DNA by MALDI-TOF. J Am Soc Mass Spectrom 15:28–31
Woods AS, Huestis MA (2001) A study of peptide-peptide interaction by matrix-assisted laser desorption/ionization. J Am Soc Mass Spectrom 12:88–96
Zehl M, Allmaier G (2003) Investigation of sample preparation and instrumental parameters in the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of noncovalent peptide/peptide complexes. Rapid Commun Mass Spectrom 17:1931–1940
Ciruela F, Burgueno J, Casado V et al (2004) Combining mass spectrometry and pull-down techniques for the study of receptor heteromerization. Direct epitope-epitope electrostatic interactions between adenosine A2A and dopamine D2 receptors. Anal Chem 76:5354–5363
Woods AS (2004) The mighty arginine, the stable quaternary amines, the powerful aromatics, and the aggressive phosphate: their role in the noncovalent minuet. J Proteome Res 3:478–484
Woods A, Zangen A (2001) A direct chemical interaction between dynorphin and excitatory amino acids. Neurochem Res 26:395–400
Masselon C, Salih B, Zenobi R (1999) Matrix-assisted laser desorption/ionization Fourier transform mass spectrometry of luteinizing hormone releasing hormone-metal ion complexes. J Am Soc Mass Spectrom 10:19–26
Friess SD, Zenobi R (2001) Protein structure information from mass spectrometry? Selective titration of arginine residues by sulfonates. J Am Soc Mass Spectrom 12:810–818
Friess SD, Daniel JM, Hartmann R et al (2002) Mass spectrometric noncovalent probing of amino acids in peptides and proteins. Int J Mass Spectrom 219:269–281
Friess SD, Daniel JM, Zenobi R (2004) Probing the surface accessibility of proteins with noncovalent receptors and MALDI mass spectrometry. Phys Chem Chem Phys 6:2664–2675
Salih B, Zenobi R (1998) MALDI mass spectrometry of dye-peptide and dye-protein complexes. Anal Chem 70:1536–1543
Greiner G, Seyfarth L, Poppitz W et al (2000) Complexation of metal ions by pseudotripeptides with different functionalized N-alkyl residues. Lett Pept Sci 7:133–141
Little DP, Jacob A, Becker T et al (1997) Direct detection of synthetic and biologically generated double-stranded DNA by MALDI-TOF MS. Int J Mass Spectrom Ion Process 169–170:323–330
Tissot B, Gonnet F, Iborra A et al (2005) Mass spectrometry analysis of the oligomeric C1q protein reveals the B chain as the target of trypsin cleavage and interaction with fucoidan. Biochemistry 44:2602–2609
Schlosser G, Pocsfalvi G, Malorni A et al (2003) Detection of immune complexes by matrix-assisted laser desorption/ionization mass spectrometry. Rapid Commun Mass Spectrom 17:2741–2747
Kiselar JG, Downard KM (2000) Preservation and detection of specific antibody-peptide complexes by matrix-assisted laser desorption ionization mass spectrometry. J Am Soc Mass Spectrom 11:746–750
Cohen SL, Chait BT (1996) Influence of matrix solution conditions on the MALDI-MS analysis of peptides and proteins. Anal Chem 68:31–37
Karas M, Hillenkamp F (1988) Laser desorption ionization of proteins with molecular masses exceeding 10000 Daltons. Anal Chem 60:2299–2301
Kussmann M, Nordhoff E, Rahbek-Nielsen H et al (1997) Matrix-assisted laser desorption/ionization mass spectrometry sample preparation techniques designed for various peptide and protein analytes. J Mass Spectrom 32:593–601
Davies GE, Stark GR (1970) Use of dimethyl suberimidate, a cross-linking reagent, in studying subunit structure of oligomeric proteins. Proc Natl Acad Sci USA 66:651–656
Evans JT, Rohrmann GF (1997) The baculovirus single-stranded DNA binding protein, LEF-3, forms a homotrimer in solution. J Virol 71:3574–3579
Helin J, Caldentey J, Kalkkinen N et al (1999) Analysis of the multimeric state of proteins by matrix assisted laser desorption/ionization mass spectrometry after cross-linking with glutaraldehyde. Rapid Commun Mass Spectrom 13:185–190
Wong SS (1991) Chemistry of protein conjugation and cross-linking. CRC, Boca Raton
Hermanson GT (2008) Bioconjugate techniques. Academic, San Diego
Pierce TS (2009) Crosslinking technical handbook. Thermo Fisher Scientific, Rockford, IL, USA
Kalkhof S, Sinz A (2008) Chances and pitfalls of chemical cross-linking with amine-reactive N-hydroxysuccinimide esters. Anal Bioanal Chem 392:305–312
Mädler S, Bich C, Touboul D et al (2009) Chemical cross-linking with NHS esters: a systematic study on amino acid reactivities. J Mass Spectrom 44:694–706
Borchers C, Tomer KB (1999) Characterization of the noncovalent complex of human immunodeficiency virus glycoprotein 120 with its cellular receptor CD4 by matrix-assisted laser desorption/ionization mass spectrometry. Biochemistry 38:11734–11740
Bich C, Scott M, Panagiotidis A et al (2008) Characterization of antibody-antigen interactions: comparison between surface plasmon resonance measurements and high-mass matrix-assisted laser desorption/ionization mass spectrometry. Anal Biochem 375:35–45
Bovet C, Ruff M, Eiler S et al (2008) Monitoring ligand modulation of protein-protein interactions by mass spectrometry: estrogen receptor α-SRC1. Anal Chem 80:7833–7839
Yanes O, Nazabal A, Wenzel R et al (2006) Detection of noncovalent complexes in biological samples by intensity fading and high-mass detection MALDI-TOF mass spectrometry. J Proteome Res 5:2711–2719
Pimenova T, Pereira CP, Schaer DJ et al (2009) Characterization of high molecular weight multimeric states of human haptoglobin and hemoglobin-based oxygen carriers by high-mass MALDI MS. J Sep Sci 32:1224–1230
Bich C, Baer S, Jecklin MC et al (2010) Probing the hydrophobic effect of noncovalent complexes by mass spectrometry. J Am Soc Mass Spectrom 21:286–289
Layh-Schmitt G, Podtelejnikov A, Mann M (2000) Proteins complexed to the P1 adhesin of Mycoplasma pneumoniae. Microbiology 146:741–747
Larsson T, Bergström J, Nilsson C et al (2000) Use of an affinity proteomics approach for the identification of low-abundant bacterial adhesins as applied on the Lewisb-binding adhesin of Helicobacter pylori. FEBS Lett 469:155–158
Woo JS, Kim DH, Allen PD et al (2008) TRPC3-interacting triadic proteins in skeletal muscle. Biochem J 411:399–405
Young MM, Tang N, Hempel JC et al (2000) High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry. Proc Natl Acad Sci USA 97:5802–5806
Schilling B, Row RH, Gibson BW et al (2003) MS2Assign, automated assignment and nomenclature of tandem mass spectra of chemically crosslinked peptides. J Am Soc Mass Spectrom 14:834–850
de Koning LJ, Kasper PT, Back JW et al (2006) Computer-assisted mass spectrometric analysis of naturally occurring and artificially introduced cross-links in proteins and protein complexes. FEBS J 273:281–291
Yang T, Horejsh DR, Mahan KJ et al (1996) Mapping cross-linking sites in modified proteins with mass spectrometry: an application to cross-linked hemoglobins. Anal Biochem 242:55–63
Soubannier V, Rusconi F, Vaillier J et al (1999) The second stalk of the yeast ATP synthase complex: identification of subunits showing cross-links with known positions of subunit 4 (subunit b). Biochemistry 38:15017–15024
Fronzes R, Chaignepain S, Bathany K et al (2003) Topological and functional study of subunit h of the F1Fo ATP synthase complex in yeast Saccharomyces cerevisiae. Biochemistry 42:12038–12049
Schäfer I, Rössle M, Biuković G et al (2006) Structural and functional analysis of the coupling subunit F in solution and topological arrangement of the stalk domains of the methanogenic A1A0 ATP synthase. J Bioenerg Biomembr 38:83–92
Rappsilber J, Siniossoglou S, Hurt EC et al (2000) A generic strategy to analyze the spatial organization of multi-protein complexes by cross-linking and mass spectrometry. Anal Chem 72:267–275
Chang Z, Kuchar J, Hausinger RP (2004) Chemical cross-linking and mass spectrometric identification of sites of interaction for UreD, UreF, and Urease. J Biol Chem 279:15305–15313
Kitatsuji C, Kurogochi M, Nishimura S-I et al (2007) Molecular basis of guanine nucleotide dissociation inhibitor activity of human neuroglobin by chemical cross-linking and mass spectrometry. J Mol Biol 368:150–160
Bennett KL, Kussmann M, Bjork P et al (2000) Chemical cross-linking with thiol-cleavable reagents combined with differential mass spectrometric peptide mapping - a novel approach to assess intermolecular protein contacts. Protein Sci 9:1503–1518
Müller DR, Schindler P, Towbin H et al (2001) Isotope-tagged cross-linking reagents. A new tool in mass spectrometric protein interaction analysis. Anal Chem 73:1927–1934
Back JW, Notenboom V, de Koning LJ et al (2002) Identification of cross-linked peptides for protein interaction studies using mass spectrometry and 18O labeling. Anal Chem 74:4417–4422
Petrotchenko EV, Olkhovik VK, Borchers CH (2005) Isotopically coded cleavable cross-linker for studying protein-protein interaction and protein complexes. Mol Cell Proteomics 4:1167–1179
Seebacher J, Mallick P, Zhang N et al (2006) Protein cross-linking analysis using mass spectrometry, isotope-coded cross-linkers, and integrated computational data processing. J Proteome Res 5:2270–2282
Ihling C, Schmidt A, Kalkhof S et al (2006) Isotope-labeled cross-linkers and Fourier transform ion cyclotron resonance mass spectrometry for structural analysis of a protein/peptide complex. J Am Soc Mass Spectrom 17:1100–1113
Sinz A (2007) Isotope-labeled photoaffinity reagents and mass spectrometry to identify protein-ligand interactions. Angew Chem Int Ed 46:660–662
Hurst GB, Lankford TK, Kennel SJ (2004) Mass spectrometric detection of affinity purified crosslinked peptides. J Am Soc Mass Spectrom 15:832–839
Pearson KM, Pannell LK, Fales HM (2002) Intramolecular cross-linking experiments on cytochrome c and ribonuclease A using an isotope multiplet method. Rapid Commun Mass Spectrom 16:149–159
Sinz A, Kalkhof S, Ihling C (2005) Mapping protein interfaces by a trifunctional cross-linker combined with MALDI-TOF and ESI-FTICR mass spectrometry. J Am Soc Mass Spectrom 16:1921–1931
Ahrends R, Kosinski J, Kirsch D et al (2006) Identifying an interaction site between MutH and the C-terminal domain of MutL by crosslinking, affinity purification, chemical coding and mass spectrometry. Nucleic Acids Res 34:3169–3180
King GJ, Jones A, Kobe B et al (2008) Identification of disulfide-containing chemical cross-links in proteins using MALDI-TOF/TOF-mass spectrometry. Anal Chem 80:5036–5043
Krauth F, Ihling CH, Rüttinger HH et al (2009) Heterobifunctional isotope-labeled amine-reactive photo-cross-linker for structural investigation of proteins by matrix-assisted laser desorption/ionization tandem time-of-flight and electrospray ionization LTQ-Orbitrap mass spectrometry. Rapid Commun Mass Spectrom 23:2811–2818
Petrotchenko EV, Xiao KH, Cable J et al (2009) BiPS, a photocleavable, isotopically coded, fluorescent cross-linker for structural proteomics. Mol Cell Proteomics 8:273–286
Paramelle D, Cantel S, Enjalbal C et al (2009) A new generation of cross-linkers for selective detection by MALDI MS. Proteomics 9:5384–5388
Steen H, Jensen ON (2002) Analysis of protein-nucleic acid interactions by photochemical cross-linking and mass spectrometry. Mass Spectrom Rev 21:163–182
Jensen ON, Barofsky DF, Young MC et al (1993) Direct observation of UV-crosslinked protein-nucleic acid complexes by matrix-assisted laser desorption ionization mass spectrometry. Rapid Commun Mass Spectrom 7:496–501
Bennett SE, Jensen ON, Barofsky DF et al (1994) UV-catalyzed cross-linking of Escherichia coli uracil-DNA glycosylase to DNA. Identification of amino acid residues in the single-stranded DNA binding site. J Biol Chem 269:21870–21879
Connor DA, Falick AM, Young MC et al (1998) Probing the binding region of the single-stranded DNA-binding domain of rat DNA polymerase beta using nanosecond-pulse laser-induced cross-linking and mass spectrometry. Photochem Photobiol 68:299–308
Wang Q, Shoeman R, Traub P (2000) Identification of the amino acid residues of the amino terminus of vimentin responsible for DNA binding by enzymatic and chemical sequencing and analysis by MALDI-TOF. Biochemistry 39:6645–6651
Urlaub H, Hartmuth K, Lührmann R (2002) A two-tracked approach to analyze RNA-protein crosslinking sites in native, nonlabeled small nuclear ribonucleoprotein particles. Methods 26:170–181
Kühn-Hölsken E, Lenz C, Sander B et al (2005) Complete MALDI-ToF MS analysis of cross-linked peptide-RNA oligonucleotides derived from nonlabeled UV-irradiated ribonucleoprotein particles. RNA 11:1915–1930
Pingoud V, Geyer H, Geyer R et al (2005) Identification of base-specific contacts in protein-DNA complexes by photocrosslinking and mass spectrometry: a case study using the restriction endonuclease SsoII. Mol Biosyst 1:135–141
Kühn-Hölsken E, Dybkov O, Sander B et al (2007) Improved identification of enriched peptide–RNA cross-links from ribonucleoprotein particles (RNPs) by mass spectrometry. Nucleic Acids Res 35:e95
Kühn-Hölsken E, Lenz C, Dickmanns A et al (2010) Mapping the binding site of snurportin 1 on native U1 snRNP by cross-linking and mass spectrometry. Nucleic Acids Res 38:5581–5593
Geyer H, Geyer R, Pingoud V (2004) A novel strategy for the identification of protein-DNA contacts by photocrosslinking and mass spectrometry. Nucleic Acids Res 32:e132
Naryshkin NA, Farrow MA, Ivanovskaya MG et al (1997) Chemical cross-linking of the human immunodeficiency virus type 1 Tat protein to synthetic models of the RNA recognition sequence TAR containing site-specific trisubstituted pyrophosphate analogues. Biochemistry 36:3496–3505
Farrow MA, Aboul-ela F, Owen D et al (1998) Site-specific cross-linking of amino acids in the basic region of Human Immunodeficiency Virus type 1 Tat peptide to chemically modified TAR RNA duplexes. Biochemistry 37:3096–3108
Qin J, Chait BT (1997) Identification and characterization of posttranslational modifications of proteins by MALDI ion trap mass spectrometry. Anal Chem 69:4002–4009
Jensen ON, Kulkarni S, Aldrich JV et al (1996) Characterization of peptide-oligonucleotide heteroconjugates by mass spectrometry. Nucleic Acids Res 24:3866–3872
Pimenova T, Nazabal A, Roschitzki B et al (2008) Epitope mapping on bovine prion protein using chemical cross-linking and mass spectrometry. J Mass Spectrom 43:185–195
Dihazi GH, Sinz A (2003) Mapping low-resolution three-dimensional protein structures using chemical cross-linking and Fourier transform ion-cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom 17:2005–2014
Gomes AF, Gozzo FC (2010) Chemical cross-linking with a diazirine photoactivatable cross-linker investigated by MALDI- and ESI-MS/MS. J Mass Spectrom 45:892–899
Onisko B, Fernández EG, Freire ML et al (2005) Probing PrPSc structure using chemical cross-linking and mass spectrometry: evidence of the proximity of Gly90 amino termini in the PrP 27–30 aggregate. Biochemistry 44:10100–10109
Mädler S, Seitz M, Robinson J et al (2010) Does chemical cross-linking with NHS esters reflect the chemical equilibrium of protein-protein noncovalent interactions in solution? J Am Soc Mass Spectrom 21:1775–1783
Kiselar JG, Downard KM (1999) Antigenic surveillance of the influenza virus by mass spectrometry. Biochemistry 38:14185–14191
Kiselar JG, Downard KM (1999) Direct identification of protein epitopes by mass spectrometry without immobilization of antibody and isolation of antibody-peptide complexes. Anal Chem 71:1792–1801
Morrissey B, Downard KM (2008) Kinetics of antigen-antibody interactions employing a MALDI mass spectrometry immunoassay. Anal Chem 80:7720–7726
Morrissey B, Downard KM (2006) A proteomics approach to survey the antigenicity of the influenza virus by mass spectrometry. Proteomics 6:2034–2041
Morrissey B, Streamer M, Downard KM (2007) Antigenic characterisation of H3N2 subtypes of the influenza virus by mass spectrometry. J Virol Methods 145:106–114
Ho JWK, Morrissey B, Downard KM (2007) A computer algorithm for the identification of protein interactions from the spectra of masses (PRISM). J Am Soc Mass Spectrom 18:563–566
Villanueva J, Yanes O, Querol E et al (2003) Identification of protein ligands in complex biological samples using intensity-fading MALDI-TOF mass spectrometry. Anal Chem 75:3385–3395
Yanes O, Villanueva J, Querol E et al (2007) Detection of non-covalent protein interactions by 'intensity fading' MALDI-TOF mass spectrometry: applications to proteases and protease inhibitors. Nat Protocol 2:119–130
Yanes O, Villanueva J, Querol E et al (2005) Functional screening of serine protease inhibitors in the medical leech Hirudo medicinalis monitored by intensity fading MALDI-TOF MS. Mol Cell Proteomics 4:1602–1613
Yanes O, Aviles FX, Roepstorff P et al (2007) Exploring the "intensity fading" phenomenon in the study of noncovalent interactions by MALDI-TOF mass spectrometry. J Am Soc Mass Spectrom 18:359–367
Shabab M, Kulkarni MJ, Khan MI (2008) Study of papain-cystatin interaction by intensity fading MALDI-TOF-MS. Protein J 27:7–12
Sanglas L, Aviles FX, Huber R et al (2009) Mammalian metallopeptidase inhibition at the defense barrier of Ascaris parasite. Proc Natl Acad Sci USA 106:1743–1747
Wang Z, Yu X, Cui M et al (2009) Investigation of calmodulin-peptide interactions using matrix-assisted laser desorption/ionization mass spectrometry. J Am Soc Mass Spectrom 20:576–583
Mishra M, Tamhane VA, Khandelwal N et al (2010) Interaction of recombinant CanPIs with Helicoverpa armigera gut proteases reveals their processing patterns, stability and efficiency. Proteomics 10:2845–2857
Gimenez-Oya V, Villacanas O, Fernandez-Busquets X et al (2009) Mimicking direct protein-protein and solvent-mediated interactions in the CDP-methylerythritol kinase homodimer: a pharmacophore-directed virtual screening approach. J Mol Model 15:997–1007
Sugaya M, Saito R, Matsumura Y et al (2008) Facile detection of specific RNA-polypeptide interactions by MALDI-TOF mass spectrometry. J Pept Sci 14:978–983
Papac DI, Hoyes J, Tomer KB (1994) Direct analysis of affinity-bound analytes by MALDI/TOF MS. Anal Chem 66:2609–2613
Papac DI, Hoyes J, Tomer KB (1994) Epitope mapping of the gastrin-releasing peptide/anti-bombesin monoclonal antibody complex by proteolysis followed by matrix-assisted laser desorption ionization mass-spectrometry. Protein Sci 3:1485–1492
Zhao YM, Muir TW, Kent SBH et al (1996) Mapping protein-protein interactions by affinity-directed mass spectrometry. Proc Natl Acad Sci USA 93:4020–4024
Parker CE, Tomer KB (2002) MALDI/MS-based epitope mapping of antigens bound to immobilized antibodies. Mol Biotechnol 20:49–62
Raska CS, Parker CE, Sunnarborg SW et al (2003) Rapid and sensitive identification of epitope-containing peptides by direct matrix-assisted laser desorption/ionization tandem mass spectrometry of peptides affinity-bound to antibody beads. J Am Soc Mass Spectrom 14:1076–1085
Schlosser G, Vékey K, Malorni A et al (2005) Combination of solid-phase affinity capture on magnetic beads and mass spectrometry to study non-covalent interactions: example of minor groove binding drugs. Rapid Commun Mass Spectrom 19:3307–3314
Rüdiger AH, Rüdiger M, Carl UD et al (1999) Affinity mass spectrometry-based approaches for the analysis of protein-protein interaction and complex mixtures of peptide-ligands. Anal Biochem 275:162–170
Legros C, Guette C, Martin-Eauclaire M-F et al (2009) Affinity capture using chimeric membrane proteins bound to magnetic beads for rapid ligand screening by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 23:745–755
Kull S, Pauly D, Störmann B et al (2010) Multiplex detection of microbial and plant toxins by immunoaffinity enrichment and matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem 82:2916–2924
Peter J, Unverzagt C, Lenz H et al (1999) Purification of prostate-specific antigen from human serum by indirect immunosorption and elution with a hapten. Anal Biochem 273:98–104
Neubert H, Jacoby ES, Bansal SS et al (2002) Enhanced affinity capture MALDI-TOF MS: orientation of an immunoglobulin G using recombinant protein G. Anal Chem 74:3677–3683
Patrie SM, Mrksich M (2007) Self-assembled monolayers for MALDI-TOF mass spectrometry for immunoassays of human protein antigens. Anal Chem 79:5878–5887
Evans-Nguyen KM, Tao S-C, Zhu H et al (2008) Protein arrays on patterned porous gold substrates interrogated with mass spectrometry: detection of peptides in plasma. Anal Chem 80:1448–1458
Johnson EM, Ellis WR, Powers LS et al (2009) Affinity capture mass spectrometry of biomarker proteins using peptide ligands from biopanning. Anal Chem 81:5999–6005
Nelson RW, Nedelkov D, Tubbs KA (2000) Biosensor chip mass spectrometry: a chip-based proteomics approach. Electrophoresis 21:1155–1163
Nelson RW, Krone JR, Jansson O (1997) Surface plasmon resonance biomolecular interaction analysis mass spectrometry. 1. Chip-based analysis. Anal Chem 69:4363–4368
Krone JR, Nelson RW, Dogruel D et al (1997) BIA/MS: interfacing biomolecular interaction analysis with mass spectrometry. Anal Biochem 244:124–132
Nelson RW, Jarvik JW, Taillon BE et al (1999) BIA/MS of epitope-tagged peptides directly from E. coli lysate: multiplex detection and protein identification at low-femtomole to subfemtomole levels. Anal Chem 71:2858–2865
Bellon S, Buchmann W, Gonnet F et al (2009) Hyphenation of surface plasmon resonance imaging to matrix-assisted laser desorption ionization mass spectrometry by on-chip mass spectrometry and tandem mass spectrometry analysis. Anal Chem 81:7695–7702
Nedelkov D, Nelson RW (2003) Design and use of multi-affinity surfaces in biomolecular interaction analysis-mass spectrometry (BIA/MS): a step toward the design of SPR/MS arrays. J Mol Recognit 16:15–19
Mehlmann M, Garvin AM, Steinwand M et al (2005) Reflectometric interference spectroscopy combined with MALDI−TOF mass spectrometry to determine quantitative and qualitative binding of mixtures of vancomycin derivatives. Anal Bioanal Chem 382:1942–1948
Wang X, Chen G, Liu H et al (2010) Four-dimensional orthogonal electrophoresis system for screening protein complexes and protein-protein interactions combined with mass spectrometry. J Proteome Res 9:5325–5334
Shevchenko A, Schaft D, Roguev A et al (2002) Deciphering protein complexes and protein interaction networks by tandem affinity purification and mass spectrometry. Mol Cell Proteomics 1:204–212
Pflieger D, Junger MA, Müller M et al (2008) Quantitative proteomic analysis of protein complexes. Mol Cell Proteomics 7:326–346
Wales TE, Engen JR (2006) Hydrogen exchange mass spectrometry for the analysis of protein dynamics. Mass Spectrom Rev 25:158–170
Mandell JG, Falick AM, Komives EA (1998) Identification of protein-protein interfaces by decreased amide proton solvent accessibility. Proc Natl Acad Sci USA 95:14705–14710
Mandell JG, Baerga-Ortiz A, Akashi S et al (2001) Solvent accessibility of the thrombin-thrombomodulin interface. J Mol Biol 306:575–589
Baerga-Ortiz A, Hughes CA, Mandell JG et al (2002) Epitope mapping of a monoclonal antibody against human thrombin by H/D-exchange mass spectrometry reveals selection of a diverse sequence in a highly conserved protein. Protein Sci 11:1300–1308
Tuma R, Coward LU, Kirk MC et al (2001) Hydrogen-deuterium exchange as a probe of folding and assembly in viral capsids. J Mol Biol 306:389–396
Hosia W, Johansson J, Griffiths WJ (2002) Hydrogen/deuterium exchange and aggregation of a polyvaline and a polyleucine alpha-helix investigated by matrix-assisted laser desorption ionization mass spectrometry. Mol Cell Proteomics 1:592–597
Nazabal A, Dos RS, Bonneu M et al (2003) Conformational transition occurring upon amyloid aggregation of the HET-s prion protein of Podospora anserina analyzed by hydrogen/deuterium exchange and mass spectrometry. Biochemistry 42:8852–8861
Kraus M, Bienert M, Krause E (2003) Hydrogen exchange studies on Alzheimer's amyloid-β peptides by mass spectrometry using matrix-assisted laser desorption/ionization and electrospray ionization. Rapid Commun Mass Spectrom 17:222–228
Nazabal A, Hornemann S, Aguzzi A et al (2009) Hydrogen/deuterium exchange mass spectrometry identifies two highly protected regions in recombinant full-length prion protein amyloid fibrils. J Mass Spectrom 44:965–977
Turner BT Jr, Maurer MC (2002) Evaluating the roles of thrombin and calcium in the activation of coagulation factor XIII using H/D exchange and MALDI-TOF MS. Biochemistry 41:7947–7954
Catalina MI, Fischer MJE, Dekker FJ et al (2005) Binding of a diphosphorylated-ITAM peptide to spleen tyrosine kinase (Syk) induces distal conformational changes: a hydrogen exchange mass spectrometry study. J Am Soc Mass Spectrom 16:1039–1051
Sabo TM, Farrell DH, Maurer MC (2006) Conformational analysis of gamma' peptide (410-427) interactions with thrombin anion binding exosite II. Biochemistry 45:7434–7445
Nazabal A, Laguerre M, Schmitter J-M et al (2003) Hydrogen/deuterium exchange on yeast ATPase supramolecular protein complex analyzed at high sensitivity by MALDI mass spectrometry. J Am Soc Mass Spectrom 14:471–481
Kipping M, Schierhorn A (2003) Improving hydrogen/deuterium exchange mass spectrometry by reduction of the back-exchange effect. J Mass Spectrom 38:271–276
Hotchko M, Anand GS, Komives EA et al (2006) Automated extraction of backbone deuteration levels from amide H/2 H mass spectrometry experiments. Protein Sci 15:583–601
Jørgensen TJD, Bache N, Roepstorff P et al (2005) Collisional activation by MALDI tandem time-of-flight mass spectrometry induces intramolecular migration of amide hydrogens in protonated peptides. Mol Cell Proteomics 4:1910–1919
Bache N, Rand KD, Roepstorff P et al (2008) Gas-phase fragmentation of peptides by MALDI in-source decay with limited amide hydrogen (1H/2H) scrambling. Anal Chem 80:6431–6435
Powell KD, Wales TE, Fitzgerald MC (2002) Thermodynamic stability measurements on multimeric proteins using a new H/D exchange- and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry-based method. Protein Sci 11:841–851
Powell KD, Ghaemmaghami S, Wang MZ et al (2002) A general mass spectrometry-based assay for the quantitation of protein-ligand binding interactions in solution. J Am Chem Soc 124:10256–10257
Ghaemmaghami S, Fitzgerald MC, Oas TG (2000) A quantitative, high-throughput screen for protein stability. Proc Natl Acad Sci USA 97:8296–8301
Ghaemmaghami S, Oas TG (2001) Quantitative protein stability measurement in vivo. Nat Struct Biol 8:879–882
Powell KD, Fitzgerald MC (2003) Accuracy and precision of a new H/D exchange- and mass spectrometry-based technique for measuring the thermodynamic properties of protein-peptide complexes. Biochemistry 42:4962–4970
West GM, Tang L, Fitzgerald MC (2008) Thermodynamic analysis of protein stability and ligand binding using a chemical modification- and mass spectrometry-based strategy. Anal Chem 80:4175–4185
West GM, Thompson JW, Soderblom EJ et al (2010) Mass spectrometry-based thermal shift assay for protein-ligand binding analysis. Anal Chem 82:5573–5581
Hofner G, Merkel D, Wanner KT (2009) MS binding assays-with MALDI toward high throughput. ChemMedChem 4:1523–1528
Acknowledgments
We would like to thank Richard Caprioli and Dobrin Nedelkov for providing original versions of figures. Financial support for this work from the Swiss National Science Foundation (grant no. 200020_124663) is gratefully acknowledged.
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Mädler, S., Erba, E.B., Zenobi, R. (2012). MALDI-ToF Mass Spectrometry for Studying Noncovalent Complexes of Biomolecules. In: Cai, Z., Liu, S. (eds) Applications of MALDI-TOF Spectroscopy. Topics in Current Chemistry, vol 331. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_311
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