Exclusively Heteronuclear NMR Experiments for the Investigation of Intrinsically Disordered Proteins: Focusing on Proline Residues

Overview

Journal Magn Reson (Gott)

Date 2023 Oct 31

PMID 37904768

Authors

Isabella C Felli

Wolfgang Bermel

Roberta Pierattelli

Affiliations

Soon will be listed here.

Abstract

NMR represents a key spectroscopic technique that contributes to the emerging field of highly flexible, intrinsically disordered proteins (IDPs) or protein regions (IDRs) that lack a stable three-dimensional structure. A set of exclusively heteronuclear NMR experiments tailored for proline residues, highly abundant in IDPs/IDRs, are presented here. They provide a valuable complement to the widely used approach based on amide proton detection, filling the gap introduced by the lack of amide protons in proline residues within polypeptide chains. The novel experiments have very interesting properties for the investigations of IDPs/IDRs of increasing complexity.

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References

Huang C, Ren G, Zhou H, Wang C . A new method for purification of recombinant human alpha-synuclein in Escherichia coli. Protein Expr Purif. 2005; 42(1):173-7. DOI: 10.1016/j.pep.2005.02.014. View

Wong L, Maier J, Wienands J, Becker S, Griesinger C . Sensitivity-Enhanced Four-Dimensional Amide-Amide Correlation NMR Experiments for Sequential Assignment of Proline-Rich Disordered Proteins. J Am Chem Soc. 2018; 140(10):3518-3522. DOI: 10.1021/jacs.8b00215. View

Piai A, Calcada E, Tarenzi T, Grande A, Varadi M, Tompa P . Just a Flexible Linker? The Structural and Dynamic Properties of CBP-ID4 Revealed by NMR Spectroscopy. Biophys J. 2016; 110(2):372-381. PMC: 4724632. DOI: 10.1016/j.bpj.2015.11.3516. View

Williamson M . The structure and function of proline-rich regions in proteins. Biochem J. 1994; 297 ( Pt 2):249-60. PMC: 1137821. DOI: 10.1042/bj2970249. View

Tossavainen H, Salovaara S, Hellman M, Ihalin R, Permi P . Dispersion from C or N: 4D experiments for backbone resonance assignment of intrinsically disordered proteins. J Biomol NMR. 2020; 74(2-3):147-159. PMC: 7080685. DOI: 10.1007/s10858-020-00299-w. View

Ahuja P, Cantrelle F, Huvent I, Hanoulle X, Lopez J, Smet C . Proline Conformation in a Functional Tau Fragment. J Mol Biol. 2015; 428(1):79-91. DOI: 10.1016/j.jmb.2015.11.023. View

Kay L . Solution NMR spectroscopy of supra-molecular systems, why bother? A methyl-TROSY view. J Magn Reson. 2011; 210(2):159-70. DOI: 10.1016/j.jmr.2011.03.008. View

Markley J, Bax A, Arata Y, Hilbers C, Kaptein R, Sykes B . Recommendations for the presentation of NMR structures of proteins and nucleic acids. IUPAC-IUBMB-IUPAB Inter-Union Task Group on the Standardization of Data Bases of Protein and Nucleic Acid Structures Determined by NMR Spectroscopy. J Biomol NMR. 1998; 12(1):1-23. DOI: 10.1023/a:1008290618449. View

Haba N, Gross R, Novacek J, Shaked H, Zidek L, Barda-Saad M . NMR determines transient structure and dynamics in the disordered C-terminal domain of WASp interacting protein. Biophys J. 2013; 105(2):481-93. PMC: 3714880. DOI: 10.1016/j.bpj.2013.05.046. View

10.

Lohr F, Pfeiffer S, Lin Y, HARTLEIB J, Klimmek O, Ruterjans H . HNCAN pulse sequences for sequential backbone resonance assignment across proline residues in perdeuterated proteins. J Biomol NMR. 2001; 18(4):337-46. DOI: 10.1023/a:1026737732576. View

11.

Shimba N, Stern A, Craik C, Hoch J, Dotsch V . Elimination of 13Calpha splitting in protein NMR spectra by deconvolution with maximum entropy reconstruction. J Am Chem Soc. 2003; 125(9):2382-3. DOI: 10.1021/ja027973e. View

12.

Alik A, Bouguechtouli C, Julien M, Bermel W, Ghouil R, Zinn-Justin S . Sensitivity-Enhanced C-NMR Spectroscopy for Monitoring Multisite Phosphorylation at Physiological Temperature and pH. Angew Chem Int Ed Engl. 2020; 59(26):10411-10415. DOI: 10.1002/anie.202002288. View

13.

Gibbs E, Lu F, Portz B, Fisher M, Medellin B, Laremore T . Phosphorylation induces sequence-specific conformational switches in the RNA polymerase II C-terminal domain. Nat Commun. 2017; 8:15233. PMC: 5437310. DOI: 10.1038/ncomms15233. View

14.

Lu K, Finn G, Lee T, Nicholson L . Prolyl cis-trans isomerization as a molecular timer. Nat Chem Biol. 2007; 3(10):619-29. DOI: 10.1038/nchembio.2007.35. View

15.

Zhou Z, Kummerle R, Qiu X, Redwine D, Cong R, Taha A . A new decoupling method for accurate quantification of polyethylene copolymer composition and triad sequence distribution with 13C NMR. J Magn Reson. 2007; 187(2):225-33. DOI: 10.1016/j.jmr.2007.05.005. View

16.

Bermel W, Bertini I, Felli I, Lee Y, Luchinat C, Pierattelli R . Protonless NMR experiments for sequence-specific assignment of backbone nuclei in unfolded proteins. J Am Chem Soc. 2006; 128(12):3918-9. DOI: 10.1021/ja0582206. View

17.

Lautenschlager J, Stephens A, Fusco G, Strohl F, Curry N, Zacharopoulou M . C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction. Nat Commun. 2018; 9(1):712. PMC: 5818535. DOI: 10.1038/s41467-018-03111-4. View

18.

Binolfi A, Rasia R, Bertoncini C, Ceolin M, Zweckstetter M, Griesinger C . Interaction of alpha-synuclein with divalent metal ions reveals key differences: a link between structure, binding specificity and fibrillation enhancement. J Am Chem Soc. 2006; 128(30):9893-901. DOI: 10.1021/ja0618649. View

19.

Schutz S, Sprangers R . Methyl TROSY spectroscopy: A versatile NMR approach to study challenging biological systems. Prog Nucl Magn Reson Spectrosc. 2020; 116:56-84. DOI: 10.1016/j.pnmrs.2019.09.004. View

20.

Furrer J, Kramer F, Marino J, Glaser S, Luy B . Homonuclear Hartmann-Hahn transfer with reduced relaxation losses by use of the MOCCA-XY16 multiple pulse sequence. J Magn Reson. 2003; 166(1):39-46. DOI: 10.1016/j.jmr.2003.09.013. View