Determination of secondary structure populations in disordered states of proteins using nuclear magnetic resonance chemical shifts.

TitleDetermination of secondary structure populations in disordered states of proteins using nuclear magnetic resonance chemical shifts.
Publication TypeJournal Article
Year of Publication2012
AuthorsCamilloni, C., A. De Simone, W. F. Vranken, and M. Vendruscolo
JournalBiochemistry
Volume51
Issue11
Pagination2224-31
Date Published2012 Mar 20
ISSN1520-4995
KeywordsBinding Sites, Nuclear Magnetic Resonance, Biomolecular, Protein Folding, Protein Structure, Secondary, Proteins
Abstract

One of the major open challenges in structural biology is to achieve effective descriptions of disordered states of proteins. This problem is difficult because these states are conformationally highly heterogeneous and cannot be represented as single structures, and therefore it is necessary to characterize their conformational properties in terms of probability distributions. Here we show that it is possible to obtain highly quantitative information about particularly important types of probability distributions, the populations of secondary structure elements (α-helix, β-strand, random coil, and polyproline II), by using the information provided by backbone chemical shifts. The application of this approach to mammalian prions indicates that for these proteins a key role in molecular recognition is played by disordered regions characterized by highly conserved polyproline II populations. We also determine the secondary structure populations of a range of other disordered proteins that are medically relevant, including p53, α-synuclein, and the Aβ peptide, as well as an oligomeric form of αB-crystallin. Because chemical shifts are the nuclear magnetic resonance parameters that can be measured under the widest variety of conditions, our approach can be used to obtain detailed information about secondary structure populations for a vast range of different protein states.

DOI10.1021/bi3001825
Alternate JournalBiochemistry
PubMed ID22360139
Grant List089703 / / Wellcome Trust / United Kingdom
/ / Biotechnology and Biological Sciences Research Council / United Kingdom
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