Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/9322
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Atom-by-atom analysis of global downhill protein folding |
Autor: | Sadqi, Mourad CSIC ORCID; Fushman, David; Muñoz, Víctor CSIC ORCID | Palabras clave: | Protein folding Three-dimensional structures Protein stability Folding kinetics Downhill folding BBL protein Escherichia coli Nuclear magnetic resonance (NMR) |
Fecha de publicación: | 14-jun-2006 | Editor: | Nature Publishing Group | Citación: | Nature 442, 317-321 (2006) | Resumen: | Protein 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. | Descripción: | 5 pages, 4 figures.-- PMID: 16799571 [PubMed].-- Supplementary information available at: http://www.nature.com/nature/journal/v442/n7100/suppinfo/nature04859.html The atomic coordinates of Naf-BBL have been deposited in the Protein Data Bank with the accession number 2QYU. |
Versión del editor: | http://dx.doi.org/10.1038/nature04859 | URI: | http://hdl.handle.net/10261/9322 | DOI: | 10.1038/nature04859 | ISSN: | 0028-0836 | E-ISSN: | 1476-4687 |
Aparece en las colecciones: | (CIB) Artículos |
Mostrar el registro completo
CORE Recommender
SCOPUSTM
Citations
224
checked on 20-abr-2024
WEB OF SCIENCETM
Citations
213
checked on 27-feb-2024
Page view(s)
355
checked on 24-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.