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Photodissociative Cross-Linking of Non-covalent Peptide-Peptide Ion Complexes in the Gas Phase

  • Huong T. H. Nguyen
  • Prokopis C. Andrikopoulos
  • Lubomír Rulíšek
  • Christopher J. Shaffer
  • František Tureček
Research Article

Abstract

We report a gas-phase UV photodissociation study investigating non-covalent interactions between neutral hydrophobic pentapeptides and peptide ions incorporating a diazirine-tagged photoleucine residue. Phenylalanine (Phe) and proline (Pro) were chosen as the conformation-affecting residues that were incorporated into a small library of neutral pentapeptides. Gas-phase ion-molecule complexes of these peptides with photo-labeled pentapeptides were subjected to photodissociation. Selective photocleavage of the diazirine ring at 355 nm formed short-lived carbene intermediates that underwent cross-linking by insertion into H–X bonds of the target peptide. The cross-link positions were established from collision-induced dissociation tandem mass spectra (CID-MS3) providing sequence information on the covalent adducts. Effects of the amino acid residue (Pro or Phe) and its position in the target peptide sequence were evaluated. For proline-containing peptides, interactions resulting in covalent cross-links in these complexes became more prominent as proline was moved towards the C-terminus of the target peptide sequence. The photocross-linking yields of phenylalanine-containing peptides depended on the position of both phenylalanine and photoleucine. Density functional theory calculations were used to assign structures of low-energy conformers of the (GLPMG + GLL*LK + H)+ complex. Born-Oppenheimer molecular dynamics trajectory calculations were used to capture the thermal motion in the complexes within 100 ps and determine close contacts between the incipient carbene and the H–X bonds in the target peptide. This provided atomic-level resolution of potential cross-links that aided spectra interpretation and was in agreement with experimental data.

Graphical Abstract

Keywords

Peptide-peptide complexes Diazirine tags Photodissociation Cross-linking Born-Oppenheimer molecular dynamics 

Notes

Funding Information

Research at University of Washington has received support from the Chemistry Division of the National Science Foundation (Grants CHE-1543805, CHE-1661815, and CHE-1624430). F.T. thanks the Klaus and Mary Ann Saegebarth Endowment for general support. Research at the IOCB Prague was supported by the Grant Agency of the Czech Republic (grant 17-24155S).

Supplementary material

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ESM 1 (PDF 2576 kb)

References

  1. 1.
    Fancy, D.A., Kodadek, T.: Chemistry for the analysis of protein–protein interactions: rapid and efficient cross-linking triggered by long wavelength light. Proc. Natl. Acad. Sci. U. S. A. 96, 6020–6024 (1999)CrossRefGoogle Scholar
  2. 2.
    Das, J.: Aliphatic diazirines as photoaffinity probes for proteins: recent developments. Chem. Rev. 111, 4405–4417 (2011)CrossRefGoogle Scholar
  3. 3.
    Singh, A., Thornton, E.R., Westheimer, F.H.: Photolysis of diazoacetylchymotrypsin. J. Biol. Chem. 237, PC3006–PC3008 (1962)Google Scholar
  4. 4.
    Fleet, G.W.J., Porter, R.R., Knowles, J.R.: Affinity labeling of antibodies with aryl nitrene as reactive group. Nature (London). 224, 511–512 (1969)CrossRefGoogle Scholar
  5. 5.
    Knowles, J.R.: Photogenerated reagents for biological receptor-site labeling. Acc. Chem. Res. 5, 155–160 (1972)CrossRefGoogle Scholar
  6. 6.
    Liu, M.T.H.: Chemistry of diazirines, vol. I and II. CRC Press, Boca Raton (1987)Google Scholar
  7. 7.
    Tomioka, H., Izawa, Y.: Photolysis of aryldiazomethanes in alcoholic matrices. Temperature and host dependencies of phenylcarbene processes in alcohols. J. Am. Chem. Soc. 99, 6128–1629 (1977)CrossRefGoogle Scholar
  8. 8.
    Senthilnathan, V.P., Platz, M.S.: Determination of the absolute rates of decays of arylcarbenes in various low temperature matrices by electron spin resonance spectroscopy. J. Am. Chem. Soc. 102, 7637–7643 (1980)CrossRefGoogle Scholar
  9. 9.
    Dix, E.J., Goodman, J.L.: Protonation of diarylcarbenes by alcohols: the importance of ion pair dynamics. J. Phys. Chem. 98, 12609–12612 (1994)CrossRefGoogle Scholar
  10. 10.
    Shaffer, C.J., Andrikopoulos, P.C., Řezáč, J., Rulíšek, L., Tureček, F.: Efficient covalent bond formation in gas-phase peptide–peptide ion complexes with the photoleucine stapler. J. Am. Soc. Mass Spectrom. 27, 633–645 (2016)CrossRefGoogle Scholar
  11. 11.
    Suchanek, M., Radzikowska, A., Thiele, C.: Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells. Nat. Methods. 2, 261–268 (2005)CrossRefGoogle Scholar
  12. 12.
    Yang, T., Li, X.-M., Bao, X., Fung, Y.M.E., Li, D.: Photolysine captures proteins that bind lysine post-traslation modifications. Nat. Chem. Biol. 12, 70 (2016)CrossRefGoogle Scholar
  13. 13.
    Pepin, R., Shaffer, C.J., Turecek, F.: Position-tunable diazirine tags for peptide-peptide ion cross-linking in the gas phase. J. Mass Spectrom. 52, 557–560 (2017)CrossRefGoogle Scholar
  14. 14.
    Sinz, A., Arlt, C., Chorev, D., Sharon, M.: Chemical cross-linking and native mass spectrometry: a fruitful combination for structural biology. Protein Sci. 24, 1193 (2015)CrossRefGoogle Scholar
  15. 15.
    Lee, S., Valentine, S.J., Reilly, J.P., Clemmer, D.E.: Controlled formation of peptide bonds in the gas phase. J. Am. Chem. Soc. 133, 15834–15837 (2011)CrossRefGoogle Scholar
  16. 16.
    McGee, W.M., McLuckey, S.A.: Efficient and directed peptide bond formation in the gas phase via ion/ion reactions. Proc. Natl. Acad. Sci. U. S. A. 111, 1288–1292 (2014)CrossRefGoogle Scholar
  17. 17.
    Koelbel, K., Warnke, S., Seo, J., von Helden, G., Moretti, R., Meiler, J., Pagel, K., Sinz, A.: Conformational shift of a β-hairpin peptide upon complex formation with an oligo-proline peptide studied by mass spectrometry. Chem. Select. 1, 3651 (2016)Google Scholar
  18. 18.
    Pezacki, J.P., Couture, P., Dunn, J.A., Warkentin, J., Wood, P.D., Lusztyk, J., Ford, F., Platz, M.S.: Rate constants for 1,2-hydrogen migration in cyclohexylidene and in substituted cyclohexylidenes. J. Org. Chem. 64, 4456 (1999)CrossRefGoogle Scholar
  19. 19.
    Schimmel, P.R., Flory, P.J.: Conformational energies and configurational statistics of copolypeptides containing L-proline. J. Mol. Biol. 34, 105–120 (1968)CrossRefGoogle Scholar
  20. 20.
    Lewis, P.N., Momany, F.A., Scheraga, H.A.: Folding of polypeptide chains in proteins: a proposed mechanism for folding. Proc Nat. Acad. Sci. U.S.A. 68, 2293–2297 (1971)CrossRefGoogle Scholar
  21. 21.
    Kuntz, I.D.: Protein folding. J. Am. Chem. Soc. 94, 4009–4012 (1972)CrossRefGoogle Scholar
  22. 22.
    Crawford, J.L., Lipscomb, W.N., Schellman, C.G.: The reverse turn as a polypeptide conformation in globular proteins. Proc. Natl. Acad. Sci. U. S. A. 70, 538–542 (1973)CrossRefGoogle Scholar
  23. 23.
    MacArthur, M.W., Thornton, J.M.: Influence of proline residues on protein conformation. J. Mol. Biol. 218, 397–412 (1991)CrossRefGoogle Scholar
  24. 24.
    Shi, L., Holliday, A.E., Bohrer, B.C., Kim, D., Servage, K.A., Russell, D.H., Clemmer, D.E.: Wet versus dry folding of polyproline. J. Am. Soc. Mass Spectrom. 27, 1037–1047 (2016)CrossRefGoogle Scholar
  25. 25.
    Basic Local Alignment Search Tool (BLAST) Available at: http://blast.ncbi.nlm.gov. Accessed 10 June 2016
  26. 26.
    Řezáč, J., Fanfrlík, J., Salahub, D., Hobza, P.: Semiempirical quantum chemical PM6 method augmented by dispersion and H-bonding correction terms reliably describes various types of noncovalent complexes. J. Chem. Theor. Comput. 5, 1749–1760 (2009)CrossRefGoogle Scholar
  27. 27.
    Janz, J.M., Ren, Y., Looby, R., Kazmi, M.A., Sachdev, P., Grunbeck, A., Haggis, L., Chinnapen, D., Lin, A.Y., Seibert, C., McMurry, T., Carlson, K.E., Muir, T.W., Hunt, S., Sakmar, T.P.: Direct interaction between an allosteric agonist pepducin and the chemokine receptor CXCR4. J. Am. Chem. Soc. 133, 15878–15881 (2011)CrossRefGoogle Scholar
  28. 28.
    Coste, J., LeNguyen, D., Castro, B.: PyBOP: a new peptide coupling reagent devoid of toxic by-product. Tetrahedron Lett. 31, 205–208 (1990)CrossRefGoogle Scholar
  29. 29.
    Shaffer, C.J., Marek, A., Nguyen, H.T.H., Tureček, F.: Combining near-UV photodissociation with electron transfer. Reduction of the diazirine ring in a photomethionine-labeled peptide ion. J. Am. Soc. Mass Spectrom. 26, 1367–1381 (2015)CrossRefGoogle Scholar
  30. 30.
    Berendsen, H.J., Postma, J.V., van Gunsteren, W.F., DiNola, A.R.H.J., Haak, J.R.: Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684–3690 (1984)CrossRefGoogle Scholar
  31. 31.
    Řezáč, J.: Cuby—ruby framework for computational chemistry, version 4, http://cuby4.molecular.cz Accessed June 2016.
  32. 32.
    Řezáč, J.: Cuby: an integrative framework for computational chemistry. J. Comput. Chem. 37, 1230–1237 (2016)CrossRefGoogle Scholar
  33. 33.
    Becke, A.D.: Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A. 38, 3098–3100 (1988)CrossRefGoogle Scholar
  34. 34.
    Lee, C., Yang, W., Parr, R.G.: Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B37, 785–789 (1988)CrossRefGoogle Scholar
  35. 35.
    Schäfer, A., Horn, H., Ahlrichs, R.: Fully optimized contracted Gaussian basis sets for atoms lithium to krypton. J. Chem. Phys. 97, 2571–2577 (1992)CrossRefGoogle Scholar
  36. 36.
    TURBOMOLE V6.6. A development of University of Karlsruhe and Forschungszentrum Karlsruhe GmbH, 1989–2014, TURBOMOLE GmbH, since 2007, available at: http://www.turbomole.com 2014. Accessed 7 June 2017
  37. 37.
    Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G.A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H.P., Izmaylov, A.F., Bloino, J., Zheng, G., Sonnenberg, J.L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery Jr., J.A., Peralta, J.E., Ogliaro, F., Bearpark, M., Heyd, J.J., Brothers, E., Kudin, K.N., Staroverov, V.N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J.C., Iyengar, S.S., Tomasi, J., Cossi, M., Rega, N., Millam, J.M., Klene, M., Knox, J.E., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Martin, R.L., Morokuma, K., Zakrzewski, V.G., Voth, G.A., Salvador, P., Dannenberg, J.J., Dapprich, S., Daniels, A.D., Farkas, O., Foresman, J.B., Ortiz, J.V., Cioslowski, J., Fox, D.J.: Gaussian 09, revision A02. Gaussian, Inc., Wallingford CT (2009)Google Scholar
  38. 38.
    Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., Nakatsuji, H., Caricato, M., Marenich, A.V., Bloino, J., Janesko, B.G., Gomperts, R., Mennucci, B., Hratchian, H.P., Ortiz, J.V., Izmaylov, A.F., Sonnenberg, J.L., Williams-Young, D., Ding, F., Lipparini, F., Egidi, F., Goings, J., Peng, B., Petrone, A., Henderson, T., Ranasinghe, D., Zakrzewski, V.G., Gao, J., Rega, N., Zheng, G., Liang, W., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Throssell, K., Montgomery Jr., J.A., Peralta, J.E., Ogliaro, F., Bearpark, M.J., Heyd, J.J., Brothers, E.N., Kudin, K.N., Staroverov, V.N., Keith, T.A., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A.P., Burant, J.C., Iyengar, S.S., Tomasi, J., Cossi, M., Millam, J.M., Klene, M., Adamo, C., Cammi, R., Ochterski, J.W., Martin, R.L., Morokuma, K., Farkas, O., Foresman, J.B., Fox, D.J.: Gaussian 16, revision A01. Gaussian, Inc., Wallingford CT (2016)Google Scholar
  39. 39.
    Chai, J.D., Head-Gordon, M.: Systematic optimization of long-range corrected hybrid density functionals. J. Chem. Phys. 128, 084106/1–084106/15 (2008)CrossRefGoogle Scholar
  40. 40.
    Chai, J.D., Head-Gordon, M.: Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys. Chem. Chem.Phys. 10, 6615–6620 (2008)CrossRefGoogle Scholar
  41. 41.
    Marek, A., Tureček, F.: Collision-induced dissociation of diazirine-labeled peptide ions. Evidence for Brønsted-acid assisted elimination of nitrogen. J. Am. Soc. Mass Spectrom. 25, 778–789 (2014)CrossRefGoogle Scholar
  42. 42.
    Schwartz, B.L., Bursey, M.M.: Some proline substituent effects in the tandem mass spectrum of protonated penta-alanine. Biol. Mass Spectrom. 21, 92–96 (1992)CrossRefGoogle Scholar
  43. 43.
    Vaisar, T., Urban, J.: Probing the proline effects in CID of protonated peptides. J. Mass Spectrom. 31, 1185–1187 (1996)CrossRefGoogle Scholar
  44. 44.
    Loo, J.A., Edmonds, C.G., Smith, R.D.: Tandem mass spectrometry of very large molecules. 2. Dissociation of multiply charged proline-containing proteins from electrospray ionization. Anal. Chem. 65, 425–438 (1993)CrossRefGoogle Scholar
  45. 45.
    Savitski, M.M., Kjeldsen, F., Nielsen, M.L., Zubarev, R.A.: Complementary sequence preferences of electron-capture dissociation and vibrational excitation in fragmentation of polypeptide polycations. Angew. Chem. Int. Ed. 45, 5301 (2006)CrossRefGoogle Scholar
  46. 46.
    Pepin, R., Laszlo, K.J., Peng, B., Marek, A., Bush, M.F., Tureček, F.: Comprehensive analysis of Gly-Leu-Gly-Gly-Lys peptide dication structures and cation-radical dissociations following electron transfer: from electron attachment to backbone cleavage, ion-molecule complexes and fragment separation. J. Phys. Chem. A. 118, 308–324 (2014)CrossRefGoogle Scholar
  47. 47.
    Tureček, F., Chen, X., Hao, C.: Where does the electron go? Electron distribution and reactivity of peptide cation-radicals formed by electron transfer in the gas phase. J. Am. Chem. Soc. 130, 8818–8833 (2008)CrossRefGoogle Scholar
  48. 48.
    Nguyen, H.T.H., Andrikopoulos, P.C., Bím, D., Rulíšek, L., Dang, A., Tureček, F.: Radical reactions affecting polar groups in threonine peptide ions. J. Phys. Chem. B. 121, 6557–6569 (2017)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Department of Chemistry, Bagley HallUniversity of WashingtonSeattleUSA
  2. 2.Institute of Organic Chemistry and BiochemistryCzech Academy of SciencesPragueCzech Republic
  3. 3.Laboratory of Biomolecular Recognition, Institute of BiotechnologyCzech Academy of SciencesVestecCzech Republic
  4. 4.Valspar CorporationMinneapolisUSA

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