Skip to main content
View expanded cover

Protein NMR pp 75–132Cite as

Relaxation Dispersion NMR Spectroscopy

Part of the Biological Magnetic Resonance book series (BIMR,volume 32)

Abstract

Relaxation dispersion nuclear magnetic resonance (NMR) spectroscopy has been developed since the 1950s and has now evolved into a very sensitive and versatile tool to study chemical and conformational exchange processes on the micro- to milliseconds (µs–ms) time scale. While relaxation dispersion NMR was originally designed with small molecules in mind, it has become a very attractive tool to also study the dynamics of biological macromolecules, after major advances had been made in hardware, experimental design and isotope labelling.

Keywords

  • NMR
  • Protein dynamics
  • Relaxation dispersion
  • Low-populated states

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-4899-7621-5_3
  • Chapter length: 58 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   119.00
Price excludes VAT (USA)
  • ISBN: 978-1-4899-7621-5
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   159.99
Price excludes VAT (USA)
Hardcover Book
USD   169.99
Price excludes VAT (USA)
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18

References

  • Allard P, Helgstrand M, Hard T (1997) A method for simulation of NOESY, ROESY, and off-resonance ROESY spectra. J Magn Reson 129(1):19–29. doi:10.1006/jmre.1997.1252

    CAS  PubMed  Google Scholar 

  • Allard P, Helgstrand M, Hard T (1998) The complete homogeneous master equation for a heteronuclear two-spin system in the basis of Cartesian product operators. J Magn Reson 134(1):7–16. doi:10.1006/jmre.1998.1509

    CAS  PubMed  Google Scholar 

  • Allerhand A, Gutowsky HS (1964) Spin-echo NMR studies of chemical exchange. I. Some general aspects. J Chem Phys 41(7):2115–2126. doi:10.1063/1.1726215

    CAS  Google Scholar 

  • Allerhand A, Gutowsky HS (1965) Spinecho studies of chemical exchange. II. Closed formulas for two sites. J Chem Phys 42(5):1587. doi:10.1063/1.1696165

    CAS  PubMed  Google Scholar 

  • Allerhand A, Chen F, Gutowsky HS (1965) Spin-echo NMR studies of chemical exchange. III. Conformational isomerization of Cyclohexane and d11-Cyclohexane. J Chem Phys 42(9):3040. doi:10.1063/1.1696376

    CAS  Google Scholar 

  • Ando I, Saito H, Tabeta R, Shoji A, Ozaki T (1984) Conformation-dependent carbon-13 NMR chemical shifts of poly(L-alanine) in the solid state: FPT INDO calculation of N-acetyl-Nʹ-methyl-L-alanine amide as a model compound of poly(L-alanine). Macromolecules 17(3):457–461. doi:10.1021/ma00133a036

    CAS  Google Scholar 

  • Auer R, Neudecker P, Muhandiram DR, Lundström P, Hansen DF, Konrat R, Kay LE (2009) Measuring the signs of 1H(alpha) chemical shift differences between ground and excited protein states by off-resonance spin-lock (R1 rho) NMR spectroscopy. J Am Chem Soc 131(31):10832–10833. doi:10.1021/ja904315m

    CAS  PubMed  Google Scholar 

  • Baldwin AJ, Hansen DF, Vallurupalli P, Kay LE (2009) Measurement of methyl axis orientations in invisible, excited states of proteins by relaxation dispersion NMR spectroscopy. J Am Chem Soc 131(33):11939–11948. doi:10.1021/ja903896p

    CAS  PubMed  Google Scholar 

  • Baldwin AJ, Religa TL, Hansen DF, Bouvignies G, Kay LE (2010) 13CHD2 methyl group probes of millisecond time scale exchange in proteins by 1H relaxation dispersion: an application to proteasome gating residue dynamics. J Am Chem Soc 132(32):10992–10995. doi:10.1021/ja104578n

    CAS  PubMed  Google Scholar 

  • Bertini I, Ciurli S, Dikiy A, Gasanov R, Luchinat C, Martini G, Safarov N (1999) High-field NMR studies of oxidized blue copper proteins: the case of spinach plastocyanin. J Am Chem Soc 121(10):2037–2046. doi:10.1021/ja983833m

    CAS  Google Scholar 

  • Bertini I, Lucinat C, Parigi G (2001). Solution NMR of paramagnetic molecules applications to metallobiomolecules and models. Elsevier, Amsterdam pp. 1–372

    Google Scholar 

  • Bloch F, Hansen WW, Packard M (1946) Nuclear induction. Phys Rev 69(3–4):127–127. doi:10.1103/PhysRev.69.127

    Google Scholar 

  • Boehr DD, Dyson HJ, Wright PE (2006a) An NMR perspective on enzyme dynamics. Chem Rev 106(8):3055–3079. doi:10.1021/cr050312q

    CAS  PubMed  Google Scholar 

  • Boehr DD, McElheny D, Dyson HJ, Wright PE (2006b) The dynamic energy landscape of dihydrofolate reductase catalysis. Science 313(5793):1638–1642. doi:10.1126/science.1130258

    CAS  PubMed  Google Scholar 

  • Boisbouvier J, Brutscher B, Simorre J-P, Marion D (1999) 13C spin relaxation measurements in RNA: sensitivity and resolution improvement using spin-state selective correlation experiments. J Biomol NMR 14(3):241–252. doi:10.1023/A:1008365712799

    CAS  Google Scholar 

  • Bouvignies G, Korzhnev DM, Neudecker P, Hansen DF, Cordes MHJ, Kay LE (2010) A simple method for measuring signs of 1H(N) chemical shift differences between ground and excited protein states. J Biomol NMR 47(2):135–141. doi:10.1007/s10858-010-9418-8

    PubMed Central  CAS  PubMed  Google Scholar 

  • Brown L, Sanctuary B (1991) Hetero-TOCSY experiments with WALTZ and DIPSI mixing sequences. J Magn Reson 91(2):413–421. doi:10.1016/0022-2364(91)90207-A

    CAS  Google Scholar 

  • Butterfoss GL, DeRose EF, Gabel SA, Perera L, Krahn JM, Mueller GA, London RE (2010) Conformational dependence of 13C shielding and coupling constants for methionine methyl groups. J Biomol NMR 48(1):31–47. doi:10.1007/s10858-010-9436-6

    CAS  PubMed  Google Scholar 

  • Carr HY, Purcell EM (1954) Effects of diffusion on free precession in nuclear magnetic resonance experiments. Phys Rev 274(1953):630–638. doi:10.1103/PhysRev.94.630

    Google Scholar 

  • Carver JP, Richards RE (1972) A general two-site solution for the chemical exchange produced dependence of T2 upon the Carr-Purcell pulse separation. J Magn Reson 6:89–105. doi:10.1016/0022-2364(72)90090-X

    CAS  Google Scholar 

  • Cavalli A, Salvatella X, Dobson CM, Vendruscolo M (2007) Protein structure determination from NMR chemical shifts. Proc Natl Acad Sci U S A 104(23):9615–9620. doi:10.1073/pnas.0610313104

    PubMed Central  CAS  PubMed  Google Scholar 

  • Clore GM, Driscoll PC, Wingfield PT, Gronenborn AM (1990) Analysis of the backbone dynamics of interleukin-1 beta using two-dimensional inverse detected heteronuclear 15N-1H NMR spectroscopy. BioChemistry 29(32):7387–7401. doi:10.1021/bi00484a006

    CAS  PubMed  Google Scholar 

  • Davis DG, Perlman ME, London RE (1994) Direct measurement of the dissociation rate constant for inhibitor enzyme complexes via the T1 rho and T2 (CPMG) methods. J Magn Reson 104:266–275. doi:10.1006/jmrb.1994.1084

    CAS  Google Scholar 

  • Dethoff EA, Petzold K, Chugh J, Casiano-Negroni A, Al-Hashimi HM (2012) Visualizing transient low-populated structures of RNA. Nature 491(7426):724–728. doi:10.1038/nature11498

    PubMed Central  CAS  PubMed  Google Scholar 

  • Deverell C, Morgan RE, Strange JH (1970) Studies of chemical exchange by nuclear magnetic relaxation in the rotating frame. Mol Phys 18(4):553–559. doi:10.1080/00268977000100611

    CAS  Google Scholar 

  • Eisenmesser EZ, Bosco DA, Akke M, Kern D (2002) Enzyme dynamics during catalysis. Science 295(5559):1520–1523. doi:10.1126/science.1066176

    CAS  PubMed  Google Scholar 

  • Eisenmesser EZ, Millet O, Labeikovsky W, Korzhnev DM, Wolf-Watz M, Bosco DA, Kern D (2005) Intrinsic dynamics of an enzyme underlies catalysis. Nature 438(7064):117–121. doi:10.1038/nature04105

    CAS  PubMed  Google Scholar 

  • Evenäs J, Malmendal A, Akke M (2001). Dynamics of the transition between open and closed conformations in a calmodulin C-terminal domain mutant. Structure 9(3):185–95. doi:10.1016/S0969-2126(01)00575-5

    Google Scholar 

  • Farber PJ, Slager J, Mittermaier AK (2012) Local folding and misfolding in the PBX homeodomain from a three-state analysis of CPMG relaxation dispersion NMR data. J Phys Chem B 116:10317–10329. doi:10.1021/jp306127m

    CAS  PubMed  Google Scholar 

  • Farrow NA, Zhang O, Forman-Kay JD, Kay LE (1994) A heteronuclear correlation experiment for simultaneous determination of 15N longitudinal decay and chemical exchange rates of systems in slow equilibrium. J Biomol NMR 4(5):727–734. doi:10.1007/BF00404280

    CAS  PubMed  Google Scholar 

  • Fawzi NL, Ying J, Ghirlando R, Torchia DA, Clore GM (2011) Atomic-resolution dynamics on the surface of amyloid-b protofibrils probed by solution NMR. Nature 480(7376):268–272. doi:10.1038/nature10577

    PubMed Central  CAS  PubMed  Google Scholar 

  • Geen H, Freeman R (1991) Band-selective radiofrequency pulses. J Magn Reson 93:93–141. doi:10.1016/0022-2364(91)90034-Q

    Google Scholar 

  • Grey MJ, Wang C, Palmer AG III (2003) Disulfide bond isomerization in basic pancreatic trypsin inhibitor: multisite chemical exchange quantified by CPMG relaxation dispersion and chemical shift modeling. J Am Chem Soc 125(47):14324–14335. doi:10.1021/ja0367389

    CAS  PubMed  Google Scholar 

  • Hahn E (1950) Spin echoes. Phys Rev 80(4):580–594. doi:10.1103/PhysRev.80.580

    Google Scholar 

  • Hansen DF, Kay LE (2007) Improved magnetization alignment schemes for spin-lock relaxation experiments. J Biomol NMR 37:245–255. doi:10.1007/s10858-006-9126-6

    CAS  PubMed  Google Scholar 

  • Hansen DF, Kay LE (2011) Determining valine side-chain rotamer conformations in proteins from methyl 13C chemical shifts: application to the 360 kDa half-proteasome. J Am Chem Soc 133(21):8272–8281. doi:10.1021/ja2014532

    CAS  PubMed  Google Scholar 

  • Hansen DF, Led JJ (2003) Implications of using approximate Bloch–McConnell equations in NMR analyses of chemically exchanging systems: application to the electron self-exchange of plastocyanin. J Magn Reson 163(2):215–227. doi:10.1016/S1090-7807(03)00062-4

    PubMed  Google Scholar 

  • Hansen DF, Led JJ (2006) Determination of the geometric structure of the metal site in a blue copper protein by paramagnetic NMR. Proc Natl Acad Sci U S A 103(6):1738–1743. doi:10.1073/pnas.0507179103

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hansen DF, Vallurupalli P, Kay LE (2008a) An improved 15N relaxation dispersion experiment for the measurement of millisecond time-scale dynamics in proteins. J Phys Chem B 112(19):5898–5904. doi:10.1021/jp074793o

    CAS  PubMed  Google Scholar 

  • Hansen DF, Vallurupalli P, Kay LE (2008b) Quantifying two-bond 1HN-13CO and one-bond 1H(alpha)-13C(alpha) dipolar couplings of invisible protein states by spin-state selective relaxation dispersion NMR spectroscopy. J Am Chem Soc 130(26):8397–8405. doi:10.1021/ja801005n

    CAS  PubMed  Google Scholar 

  • Hansen DF, Vallurupalli P, Lundström P, Neudecker P, Kay LE (2008c) Probing chemical shifts of invisible states of proteins with relaxation dispersion NMR spectroscopy: How well can we do? J Am Chem Soc 130(8):2667–2675. doi:10.1021/ja078337p

    CAS  PubMed  Google Scholar 

  • Hansen AL, Nikolova EN, Casiano-Negroni A, Al-Hashimi HM (2009a) Extending the range of microsecond-to-millisecond chemical exchange detected in labeled and unlabeled nucleic acids by selective carbon R(1rho) NMR spectroscopy. J Am Chem Soc 131(11):3818–3819. doi:10.1021/ja8091399

    CAS  PubMed  Google Scholar 

  • Hansen DF, Vallurupalli P, Kay LE (2009b) Measurement of methyl group motional parameters of invisible, excited protein states by NMR spectroscopy. J Am Chem Soc 131(35):12745–12754. doi:10.1021/ja903897e

    CAS  PubMed  Google Scholar 

  • Hansen DF, Neudecker P, Kay LE (2010a) Determination of isoleucine side-chain conformations in ground and excited states of proteins from chemical shifts. J Am Chem Soc 132(22):7589–7591. doi:10.1021/ja102090z

    CAS  PubMed  Google Scholar 

  • Hansen DF, Neudecker P, Vallurupalli P, Mulder FAA, Kay LE (2010b) Determination of Leu side-chain conformations in excited protein states by NMR relaxation dispersion. J Am Chem Soc 132(1):42–43. doi:10.1021/ja909294n

    CAS  PubMed  Google Scholar 

  • Hansen DF, Westler W, Kunze M, Markley J, Weinhold F, Led JJ (2012) Accurate structure and dynamics of the metal-site of paramagnetic metalloproteins from NMR parameters using natural bond orbitals. J Am Chem Soc 134(10):4670–4682. doi:10.1021/ja209348p

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hass MA, Hansen DF, Christensen HE, Led JJ, Kay LE (2008) Characterization of conformational exchange of a histidine side chain: protonation, rotamerization, and tautomerization of His61 in plastocyanin from Anabaena variabilis. J Am Chem Soc 130(26):8460–8470. doi:10.1021/ja801330h

    CAS  PubMed  Google Scholar 

  • Henzler-Wildman KA, Kern D (2007a) Dynamic personalities of proteins. Nature 450(7172):964–972. doi:10.1038/nature06522

    CAS  PubMed  Google Scholar 

  • Henzler-Wildman KA, Thai V, Lei M, Ott M, Wolf-Watz M, Fenn T, Kern D (2007b) Intrinsic motions along an enzymatic reaction trajectory. Nature 450(7171):838–844. doi:10.1038/nature06410

    CAS  PubMed  Google Scholar 

  • Hill RB, Bracken C, DeGrado WF, Palmer AG III (2000) Molecular motions and protein folding: characterization of the backbone dynamics and folding equilibrium of α 2 D using 13 C NMR spin relaxation. J Am Chem Soc 122(47):11610–11619. doi:10.1021/ja001129b

    CAS  Google Scholar 

  • Hoogstraten CG, Wank JR, Pardi A (2000) Active site dynamics in the lead-dependent ribozyme. Biochemistry 39(32):9951–9958. doi:10.1021/bi0007627

    CAS  PubMed  Google Scholar 

  • Igumenova TI, Brath U, Akke M, Palmer AG III (2007) Characterization of chemical exchange using residual dipolar coupling. J Am Chem Soc 129(44):13396–13397. doi:10.1021/ja0761636

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ishima R, Torchia DA (2003) Extending the range of amide proton relaxation dispersion experiments in proteins using a constant-time relaxation-compensated CPMG approach. J Biomol NMR 25(3):243–248. doi:10.1023/A:1022851228405

    CAS  PubMed  Google Scholar 

  • Ishima R, Baber J, Louis JM, Torchia DA (2004) Carbonyl carbon transverse relaxation dispersion measurements and ms-μs timescale motion in a protein hydrogen bond network. J Biomol NMR 29(2):187–198. doi:10.1023/B:JNMR.0000019249.50306.5d

    CAS  PubMed  Google Scholar 

  • Kay LE, Torchia DA, Bax A (1989) Backbone dynamics of proteins as studied by 15N inverse detected heteronuclear NMR spectroscopy: application to staphylococcal nuclease. Biochemistry 28(23):8972–8979. doi:10.1021/bi00449a003

    CAS  PubMed  Google Scholar 

  • Kay LE, Bull T, Nicholson L, Griesinger C, Schwalbe H, Bax A, Torchia D (1992) The measurement of heteronuclear transverse relaxation times in ax3 spin systems via polarization-transfer techniques. J Magn Reson 100(3):538–558. doi:10.1016/0022-2364(92)90058-F

    CAS  Google Scholar 

  • Koerdel J, Skelton NJ, Akke M, Palmer AG III, Chazin WJ (1992) Backbone dynamics of calcium-loaded calbindin D9k studied by two-dimensional proton-detected nitrogen-15 NMR spectroscopy. Biochemistry 31(20):4856–4866. doi:10.1021/bi00135a017

    CAS  Google Scholar 

  • Kontaxis G, Bax A (2001) Multiplet component separation for measurement of methyl 13C-1H dipolar couplings in weakly aligned proteins. J Biomol NMR 20(1):77–82. doi:10.1023/A:1011280529850

    CAS  PubMed  Google Scholar 

  • Korzhnev DM, Kloiber K, Kay LE (2004a) Multiple-quantum relaxation dispersion NMR spectroscopy probing millisecond time-scale dynamics in proteins: theory and application. J Am Chem Soc 126(23):7320–7329. doi:10.1021/ja049968b

    CAS  PubMed  Google Scholar 

  • Korzhnev DM, Salvatella X, Vendruscolo M, Di Nardo AA, Davidson AR, Dobson CM, Kay LE (2004b) Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR. Nature 430(6999):586–590. doi:10.1038/nature02655

    CAS  PubMed  Google Scholar 

  • Korzhnev DM, Neudecker P, Mittermaier A, Orekhov VY, Kay LE (2005a) Multiple-site exchange in proteins studied with a suite of six NMR relaxation dispersion experiments: an application to the folding of a Fyn SH3 domain mutant. J Am Chem Soc 127(44):15602–15611. doi:10.1021/ja054550e

    CAS  PubMed  Google Scholar 

  • Korzhnev DM, Orekhov VY, Kay LE (2005b) Off-resonance R1 rho NMR studies of exchange dynamics in proteins with low spin-lock fields: an application to a Fyn SH3 domain. J Am Chem Soc 127(2):713–721. doi:10.1021/ja0446855

    CAS  PubMed  Google Scholar 

  • Korzhnev DM, Bezsonova I, Evanics F, Taulier N, Zhou Z, Bai Y, Kay LE (2006) Probing the transition state ensemble of a protein folding reaction by pressure-dependent NMR relaxation dispersion. J Am Chem Soc 128(15):5262–5269. doi:10.1021/ja0601540

    CAS  PubMed  Google Scholar 

  • Korzhnev DM, Religa TL, Lundström P, Fersht AR, Kay LE (2007) The folding pathway of an FF domain: characterization of an on-pathway intermediate state under folding conditions by 15N, 13Cα and 13C-methyl relaxation dispersion and 1H/2H-exchange NMR spectroscopy. J Mol Biol 372(2):497–512. doi:10.1016/j.jmb.2007.06.012

    CAS  PubMed  Google Scholar 

  • Korzhnev DM, Religa TL, Banachewicz W, Fersht AR, Kay LE (2010) A transient and low-populated protein-folding intermediate at atomic resolution. Science 329(5997):1312–1316. doi:10.1126/science.1191723

    CAS  PubMed  Google Scholar 

  • Kristensen SM, Siegal G, Sankar A, Driscoll PC (2000) Backbone dynamics of the C-terminal SH2 domain of the p85alpha subunit of phosphoinositide 3-kinase: effect of phosphotyrosine-peptide binding and characterization of slow conformational exchange processes. J Mol Biol 299(3):771–788. doi:10.1006/jmbi.2000.3760

    CAS  PubMed  Google Scholar 

  • Kupce E, Freeman R (1995) Adiabatic pulses for wideband inversion and broadband decoupling. J Magn Reson 115:273–276. doi:10.1006/jmra.1995.1179

    CAS  Google Scholar 

  • Latham MP, Brown DJ, McCallum SA, Pardi A (2005). NMR methods for studying the structure and dynamics of RNA. ChemBiolChem 6(9):1492–1505. doi:10.1002/cbic.200500123

    CAS  Google Scholar 

  • Le H, Oldfield E (1994) Correlation between 15N NMR chemical shifts in proteins and secondary structure. J Biomol NMR 4(3):341–348. doi:10.1007/BF00179345

    CAS  PubMed  Google Scholar 

  • Lim KH, Dyson HJ, Kelly JW, Wright PE (2013) Localized structural fluctuations promote amyloidogenic conformations in transthyretin. J Mol Biol 425(6):977–988. doi:10.1016/j.jmb.2013.01.008

    PubMed Central  CAS  PubMed  Google Scholar 

  • London RE, Wingad BD, Mueller GA (2008) Dependence of amino acid side chain 13C shifts on dihedral angle: application to conformational analysis. J Am Chem Soc 130(33):11097–11105. doi:10.1021/ja802729t

    PubMed Central  CAS  PubMed  Google Scholar 

  • Loria JP, Rance M, Palmer AG III (1999a) A relaxation-compensated Carr–Purcell–Meiboom–Gill sequence for characterizing chemical exchange by NMR spectroscopy. J Am Chem Soc 121(10):2331–2332. doi:10.1021/ja983961a

    CAS  Google Scholar 

  • Loria JP, Rance M, Palmer AG III (1999b) A TROSY CPMG sequence for characterizing chemical exchange in large proteins. J Biomol NMR 15(2):151–155. doi:10.1023/A:1008355631073

    CAS  PubMed  Google Scholar 

  • Lundström P, Akke M (2005) Off-resonance rotating-frame amide proton spin relaxation experiments measuring microsecond chemical exchange in proteins. J Biomol NMR 32(2):163–173. doi:10.1007/s10858-005-5027-3

    PubMed  Google Scholar 

  • Lundström P, Teilum K, Carstensen T, Bezsonova I, Wiesner S, Hansen DF, Kay LE (2007a) Fractional 13C enrichment of isolated carbons using [1-13C]- or [2- 13C]-glucose facilitates the accurate measurement of dynamics at backbone Calpha and side-chain methyl positions in proteins. J Biomol NMR 38(3):199–212. doi:10.1007/s10858-007-9158-6

    PubMed  Google Scholar 

  • Lundström P, Vallurupalli P, Religa TL, Dahlquist FW, Kay LE (2007b) A single-quantum methyl C-13-relaxation dispersion experiment with improved sensitivity. J Biomol NMR 38(1):79–88. doi:10.1007/s10858-007-9149-7

    PubMed  Google Scholar 

  • Lundström P, Hansen DF, Kay LE (2008) Measurement of carbonyl chemical shifts of excited protein states by relaxation dispersion NMR spectroscopy: comparison between uniformly and selectively 13C labeled samples. J Biomol NMR 42(1):35–47. doi:10.1007/s10858-008-9260-4

    PubMed  Google Scholar 

  • Lundström P, Hansen DF, Vallurupalli P, Kay LE (2009a) Accurate measurement of alpha proton chemical shifts of excited protein states by relaxation dispersion NMR spectroscopy. J Am Chem Soc 131(5):1915–1926. doi:10.1021/ja807796a

    PubMed  Google Scholar 

  • Lundström P, Vallurupalli P, Hansen DF, Kay LE (2009b) Isotope labeling methods for studies of excited protein states by relaxation dispersion NMR spectroscopy. Nat Protoc 4(11):1641–1648. doi:10.1038/nprot.2009.118

    PubMed  Google Scholar 

  • Luz Z, Meiboom S (1963) Trimethylammonium ion in aqueous solution—order of the reaction with respect to solvent. J Chem Phys 39(2):366–370. doi:10.1063/1.1734254

    CAS  Google Scholar 

  • Massi F, Grey MJ, Palmer AG III (2005) Microsecond timescale backbone conformational dynamics in ubiquitin studied with NMR R1p rho relaxation experiments. Protein Sci 14(3):735–742. doi:10.1110/ps.041139505

    PubMed Central  CAS  PubMed  Google Scholar 

  • McConnell HM (1958) Reaction rates by nuclear magnetic resonance. J Chem Phys 28(3):430. doi:10.1063/1.1744152

    CAS  Google Scholar 

  • Meiboom S, Gill D (1958) Modified spin-echo method for measuring nuclear relaxation times. Rev Sci Instrum 29(8):688. doi:10.1063/1.1716296

    CAS  Google Scholar 

  • Meinhold DW, Wright PE (2011) Measurement of protein unfolding/refolding kinetics and structural characterization of hidden intermediates by NMR relaxation dispersion. Proc Natl Acad Sci U S A 108(22):9078–9083. doi:10.1073/pnas.1105682108

    PubMed Central  CAS  PubMed  Google Scholar 

  • Morrison EA, DeKoster GT, Dutta S, Vafabakhsh R, Clarkson MW, Bahl A, Henzler-Wildman KA (2012) Antiparallel EmrE exports drugs by exchanging between asymmetric structures. Nature 481(7379):45–50. doi:10.1038/nature10703

    CAS  Google Scholar 

  • Mulder FAA, Spronk CA, Slijper M, Kaptein R, Boelens R (1996) Improved HSQC experiments for the observation of exchange broadened signals. J Biomol NMR 8(2):223–228. doi:10.1007/BF00211169

    CAS  PubMed  Google Scholar 

  • Mulder FAA, Mittermaier A, Hon B, Dahlquist FW, Kay LE (2001a) Studying excited states of proteins by NMR spectroscopy. Nat Struct Biol 8(11):932–935. doi:10.1038/nsb1101-932

    CAS  PubMed  Google Scholar 

  • Mulder FAA, Skrynnikov NR, Hon B, Dahlquist FW, Kay LE (2001b) Measurement of slow (μs-ms) time scale dynamics in protein side chains by 15N relaxation dispersion NMR spectroscopy: application to Asn and Gln residues in a cavity mutant of T4 lysozyme. J Am Chem Soc 123(5):967–975

    CAS  PubMed  Google Scholar 

  • Neal S, Nip AM, Zhang H, Wishart DS (2003) Rapid and accurate calculation of protein 1H, 13C and 15N chemical shifts. J Biomol NMR 26(3):215–240. doi:10.1023/A:1023812930288

    CAS  PubMed  Google Scholar 

  • Neudecker P, Zarrine-Afsar A, Davidson AR, Kay LE (2007) Phi-value analysis of a three-state protein folding pathway by NMR relaxation dispersion spectroscopy. Proc Natl Acad Sci U S A 104(40):15717–15722. doi:10.1073/pnas.0705097104

    PubMed Central  CAS  PubMed  Google Scholar 

  • Neudecker P, Robustelli P, Cavalli A, Walsh P, Lundström P, Zarrine-Afsar A, Kay LE (2012) Structure of an intermediate state in protein folding and aggregation. Science 336(6079):362–366. doi:10.1126/science.1214203

    CAS  PubMed  Google Scholar 

  • Nikolova EN, Kim E, Wise AA, O’Brien PJ, Andricioaei I, Al-Hashimi HM (2011) Transient Hoogsteen base pairs in canonical duplex DNA. Nature 470(7335):498–502. doi:10.1038/nature09775

    PubMed Central  CAS  PubMed  Google Scholar 

  • Orekhov VY, Pervushin KV, Arseniev AS (1994) Backbone dynamics of (1-71)bacterioopsin studied by two-dimensional 1H-15N NMR spectroscopy. Eur J Biochem 219(3):887–896. doi:10.1111/j.1432-1033.1994.tb18570.x

    CAS  PubMed  Google Scholar 

  • Orekhov VY, Korzhnev DM, Kay LE (2004) Double- and zero-quantum NMR relaxation dispersion experiments sampling millisecond time scale dynamics in proteins. J Am Chem Soc 126(6):1886–1891. doi:10.1021/ja038620y

    CAS  PubMed  Google Scholar 

  • Ottiger M, Delaglio F, Bax A (1998). Measurement of J and dipolar couplings from simplified two-dimensional NMR spectra. J Magn Reson 131(2):373–378. doi:10.1006/jmre.1998.1361

    CAS  Google Scholar 

  • Palmer AG III, Massi F (2006) Characterization of the dynamics of biomacromolecules using rotating-frame spin relaxation NMR spectroscopy. Chem Rev 106(5):1700–1719. doi:10.1021/cr0404287

    CAS  PubMed  Google Scholar 

  • Pervushin KV, Riek R, Wider G, Wüthrich K (1997) Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution. Proc Natl Acad Sci U S A 94(23):12366–12371. doi:10.1073/pnas.94.23.12366

    PubMed Central  CAS  PubMed  Google Scholar 

  • Purcell EM, Torrey HC, Pound RV (1946) Resonance absorption by nuclear magnetic moments in a solid. Phys Rev 69(1–2):37–38. doi:10.1103/PhysRev.69.37

    CAS  Google Scholar 

  • Shen Y, Bax A (2007) Protein backbone chemical shifts predicted from searching a database for torsion angle and sequence homology. J Biomol NMR 38(4):289–302. doi:10.1007/s10858-007-9166-6

    CAS  PubMed  Google Scholar 

  • Shen Y, Lange O, Delaglio F, Rossi P, Aramini JM, Liu G, Bax A (2008) Consistent blind protein structure generation from NMR chemical shift data. Proc Natl Acad Sci U S A 105(12):4685–4690. doi:10.1073/pnas.0800256105

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shen Y, Delaglio F, Cornilescu G, Bax A (2009) TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J Biomol NMR 44(4):213–223. doi:10.1007/s10858-009-9333-z

    PubMed Central  CAS  PubMed  Google Scholar 

  • Skrynnikov NR, Mulder FAA, Hon B, Dahlquist FW, Kay LE (2001) Probing slow time scale dynamics at methyl-containing side chains in proteins by relaxation dispersion NMR measurements: application to methionine residues in a cavity mutant of T4 lysozyme. J Am Chem Soc 123(19):4556–4566. doi:10.1021/ja004179p

    CAS  PubMed  Google Scholar 

  • Skrynnikov NR, Dahlquist FW, Kay LE (2002) Reconstructing NMR spectra of “invisible” excited protein states using HSQC and HMQC experiments. J Am Chem Soc 124(41):12352–12360. doi:10.1021/ja0207089

    CAS  PubMed  Google Scholar 

  • Sørensen OW, Eich GW, Levitt MH, Bodenhausen G, Ernst RR (1983) Product operator formalism for the description of NMR pulse experiments. Prog NMR Spectrosc 16:163–192 doi:10.1016/0079-6565(84)80005-9

    Google Scholar 

  • Spera S, Bax A (1991) Empirical correlation between protein backbone conformation and C.alpha. and C.beta. 13C nuclear magnetic resonance chemical shifts. J Am Chem Soc 113(14):5490–5492. doi:10.1021/ja00014a071

    CAS  Google Scholar 

  • Sprangers R, Kay LE (2007) Quantitative dynamics and binding studies of the 20S proteasome by NMR. Nature 445(7128):618–622. doi:10.1038/nature05512

    CAS  PubMed  Google Scholar 

  • Stone MJ, Chandrasekhar K, Holmgren A, Wright PE, Dyson HJ (1993) Comparison of backbone and tryptophan side-chain dynamics of reduced and oxidized Escherichia coli thioredoxin using nitrogen-15 NMR relaxation measurements. Biochemistry 32(2):426–435. doi:10.1021/bi00053a007

    CAS  PubMed  Google Scholar 

  • Sugase K, Dyson HJ, Wright PE (2007) Mechanism of coupled folding and binding of an intrinsically disordered protein. Nature 447(7147):1021–1025. doi:10.1038/nature05858

    CAS  PubMed  Google Scholar 

  • Szyperski T, Luginbühl P, Otting G, Güntert P, Wüthrich K (1993). Protein dynamics studied by rotating frame 15N spin relaxation times. J Biomol NMR, 3(2). doi:10.1007/BF00178259

    Google Scholar 

  • Tollinger M, Skrynnikov NR, Mulder FAA, Forman-Kay JD, Kay LE (2001) Slow dynamics in folded and unfolded states of an SH3 domain. J Am Chem Soc 123(46):11341–11352. doi:10.1021/ja011300z

    CAS  PubMed  Google Scholar 

  • Tollinger M, Sivertsen AC, Meier BH, Ernst M, Schanda P (2012) Site-resolved measurement of microsecond-to-millisecond conformational-exchange processes in proteins by solid-state NMR spectroscopy. J Am Chem Soc 134(36):14800–14807. doi:10.1021/ja303591y

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tzeng S-R, Kalodimos CG (2009) Dynamic activation of an allosteric regulatory protein. Nature 462(7271):368–372. doi:10.1038/nature08560

    CAS  PubMed  Google Scholar 

  • Vallurupalli P, Kay LE (2006) Complementarity of ensemble and single-molecule measures of protein motion: a relaxation dispersion NMR study of an enzyme complex. Proc Natl Acad Sci U S A 103(32):11910–11915. doi:10.1073/pnas.0602310103

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vallurupalli P, Hansen DF, Stollar E, Meirovitch E, Kay LE (2007a) Measurement of bond vector orientations in invisible excited states of proteins. Proc Natl Acad Sci U S A 104(47):18473–18477. doi:10.1073/pnas.0708296104

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vallurupalli P, Scott L, Williamson JR, Kay LE (2007b) Strong coupling effects during X-pulse CPMG experiments recorded on heteronuclear ABX spin systems: artifacts and a simple solution. J Biomol NMR 38(1):41–46. doi:10.1007/s10858-006-9139-1

    CAS  PubMed  Google Scholar 

  • Vallurupalli P, Hansen DF, Kay LE (2008a) Probing structure in invisible protein states with anisotropic NMR chemical shifts. J Am Chem Soc 130(9):2734–2735. doi:10.1021/ja710817g

    CAS  PubMed  Google Scholar 

  • Vallurupalli P, Hansen DF, Kay LE (2008b) Structures of invisible, excited protein states by relaxation dispersion NMR spectroscopy. Proc Natl Acad Sci U S A 105(33):11766–11771. doi:10.1073/pnas.0804221105

    PubMed Central  CAS  PubMed  Google Scholar 

  • Vallurupalli P, Hansen DF, Lundström P, Kay LE (2009) CPMG relaxation dispersion NMR experiments measuring glycine 1H alpha and 13C alpha chemical shifts in the “invisible” excited states of proteins. J Biomol NMR 45(1–2):45–55. doi:10.1007/s10858-009-9310-6

    CAS  PubMed  Google Scholar 

  • Vallurupalli P, Bouvignies G, Kay LE (2012) Studying “invisible” excited protein states in slow exchange with a major state conformation. J Am Chem Soc 134(19):8148–8161. doi:10.1021/ja3001419

    CAS  PubMed  Google Scholar 

  • Wang C, Grey MJ, Palmer AG III (2001) CPMG sequences with enhanced sensitivity to chemical exchange. J Biomol NMR 21(4):361–366. doi:10.1023/A:1013328206498

    CAS  PubMed  Google Scholar 

  • Ward KM, Aletras AH, Balaban RS (2000) A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson 143(1):79–87. doi:10.1006/jmre.1999.1956

    CAS  PubMed  Google Scholar 

  • Wells EJ, Gutowsky HS (1965) NMR spin-echo trains for a coupled two-spin system. J Chem Phys 43(9):3414. doi:10.1063/1.1726421

    CAS  Google Scholar 

  • Wishart DS, Case DA (2001) Use of chemical shifts in macromolecular structure determination. Methods Enzymol 338:3–34 doi:10.1016/S0076-6879(02)38214-4

    CAS  PubMed  Google Scholar 

  • Wishart DS, Sykes BD (1994) The 13C chemical-shift index: a simple method for the identification of protein secondary structure using 13C chemical-shift data. J Biomol NMR 4:171–180 doi:10.1007/BF00175245

    CAS  PubMed  Google Scholar 

  • Wolf-Watz M, Thai V, Henzler-Wildman KA, Hadjipavlou G, Eisenmesser EZ, Kern D (2004) Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair. Nat Struct Mol Biol 11(10):945–949. doi:10.1038/nsmb821

    CAS  PubMed  Google Scholar 

  • Xu X-P, Case DA (2002) Probing multiple effects on 15N, 13C alpha, 13C beta, and 13C’ chemical shifts in peptides using density functional theory. Biopolymers 65(6):408–423. doi:10.1002/bip.10276

    CAS  PubMed  Google Scholar 

  • Zuiderweg ER (1990) Analysis of multiple-pulse-based heteronuclear J cross polarization in liquids. J Magn Reson 89(3):533–542. doi:10.1016/0022-2364(90)90336-8

    CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC)

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Flemming Hansen .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2015 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Sauerwein, A., Hansen, D. (2015). Relaxation Dispersion NMR Spectroscopy. In: Berliner, L. (eds) Protein NMR. Biological Magnetic Resonance, vol 32. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7621-5_3

Download citation