Please use this identifier to cite or link to this item:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Atom-by-atom analysis of global downhill protein folding

AuthorsSadqi, Mourad; Fushman, David; Muñoz, Víctor
KeywordsProtein folding
Three-dimensional structures
Protein stability
Folding kinetics
Downhill folding
BBL protein
Escherichia coli
Nuclear magnetic resonance (NMR)
Issue Date14-Jun-2006
PublisherNature Publishing Group
CitationNature 442, 317-321 (2006)
AbstractProtein folding is an inherently complex process involving coordination of the intricate networks of weak interactions that stabilize native three-dimensional structures. In the conventional paradigm, simple protein structures are assumed to fold in an all-or-none process that is inaccessible to experiment. Existing experimental methods therefore probe folding mechanisms indirectly. A widely used approach interprets changes in protein stability and/or folding kinetics, induced by engineered mutations, in terms of the structure of the native protein. In addition to limitations in connecting energetics with structure, mutational methods have significant experimental uncertainties and are unable to map complex networks of interactions. In contrast, analytical theory predicts small barriers to folding and the possibility of downhill folding. These theoretical predictions have been confirmed experimentally in recent years, including the observation of global downhill folding. However, a key remaining question is whether downhill folding can indeed lead to the high-resolution analysis of protein folding processes. Here we show, with the use of nuclear magnetic resonance (NMR), that the downhill protein BBL from Escherichia coli unfolds atom by atom starting from a defined three-dimensional structure. Thermal unfolding data on 158 backbone and side-chain protons out of a total of 204 provide a detailed view of the structural events during folding. This view confirms the statistical nature of folding, and exposes the interplay between hydrogen bonding, hydrophobic forces, backbone conformation and side-chain entropy. From the data we also obtain a map of the interaction network in this protein, which reveals the source of folding cooperativity. Our approach can be extended to other proteins with marginal barriers (less than 3RT), providing a new tool for the study of protein folding.
Description5 pages, 4 figures.-- PMID: 16799571 [PubMed].-- Supplementary information available at:
The atomic coordinates of Naf-BBL have been deposited in the Protein Data Bank with the accession number 2QYU.
Publisher version (URL)
Appears in Collections:(CIB) Artículos

Show full item record
Review this work


checked on May 16, 2022


checked on May 12, 2022

Page view(s)

checked on May 19, 2022

Google ScholarTM




WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.