Quantitative residue-specific protein backbone torsion angle dynamics from concerted measurement of 3J couplings.

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TitleQuantitative residue-specific protein backbone torsion angle dynamics from concerted measurement of 3J couplings.
Publication TypeJournal Article
Year of Publication2015
AuthorsLee, JHo, Li, F, Grishaev, A, Bax, A
JournalJ Am Chem Soc
Volume137
Issue4
Pagination1432-5
Date Published2015 Feb 4
ISSN1520-5126
KeywordsAlgorithms, alpha-Synuclein, Animals, Entropy, Humans, Nuclear Magnetic Resonance, Biomolecular, Peptides, Protein Conformation, Protein Folding, Proteins, Ubiquitin
Abstract

Three-bond (3)J(C'C') and (3)J(HNHα) couplings in peptides and proteins are functions of the intervening backbone torsion angle ϕ. In well-ordered regions, (3)J(HNHα) is tightly correlated with (3)J(C'C'), but the presence of large ϕ angle fluctuations differentially affects the two types of couplings. Assuming the ϕ angles follow a Gaussian distribution, the width of this distribution can be extracted from (3)J(C'C') and (3)J(HNHα), as demonstrated for the folded proteins ubiquitin and GB3. In intrinsically disordered proteins, slow transverse relaxation permits measurement of (3)J(C'C') and (3)J(HNH) couplings at very high precision, and impact of factors other than the intervening torsion angle on (3)J will be minimal, making these couplings exceptionally valuable structural reporters. Analysis of α-synuclein yields rather homogeneous widths of 69 ± 6° for the ϕ angle distributions and (3)J(C'C') values that agree well with those of a recent maximum entropy analysis of chemical shifts, J couplings, and (1)H-(1)H NOEs. Data are consistent with a modest (≤30%) population of the polyproline II region.

DOI10.1021/ja512593s
Alternate JournalJ. Am. Chem. Soc.
PubMed ID25590347
PubMed Central IDPMC4318723
Grant ListZIA DK029047-08 / / Intramural NIH HHS / United States