Direct observation of an ensemble of stable collapsed states in the mechanical folding of ubiquitin

Statistical theories of protein folding have long predicted plausible mechanisms for reducing the vast conformational space through distinct ensembles of structures. However, these predictions have remained untested by bulk techniques, because the conformational diversity of folding molecules has be...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 106; no. 26; pp. 10534 - 10539
Main Authors Garcia-Manyes, Sergi, Dougan, Lorna, Badilla, Carmen L, Brujić, Jasna, Fernández, Julio M
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 30.06.2009
National Acad Sciences
Subjects
Collapsed states
Computer Simulation
energy
hydrophobicity
Kinetics
mechanics
Microscopy, Atomic Force - methods
Models, Chemical
Molecular structure
Molecules
Physical Sciences
Polyproteins
prediction
Protein Conformation
Protein Denaturation
Protein Folding
Protein refolding
Proteins
Spectroscopy
Spectrum analysis
Statistical theories
Thermodynamics
Trajectories
ubiquitin
Ubiquitin - chemistry
Ubiquitins
Online AccessGet full text

Cover

More Information
Summary:Statistical theories of protein folding have long predicted plausible mechanisms for reducing the vast conformational space through distinct ensembles of structures. However, these predictions have remained untested by bulk techniques, because the conformational diversity of folding molecules has been experimentally unapproachable. Owing to recent advances in single molecule force-clamp spectroscopy, we are now able to probe the structure and dynamics of the small protein ubiquitin by measuring its length and mechanical stability during each stage of folding. Here, we discover that upon hydrophobic collapse, the protein rapidly selects a subset of minimum energy structures that are mechanically weak and essential precursors of the native fold. From this much reduced ensemble, the native state is acquired through a barrier-limited transition. Our results support the validity of statistical mechanics models in describing the folding of a small protein on biological timescales.
Bibliography:SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 14
ObjectType-Article-1
ObjectType-Feature-2
content type line 23
2Present address: School of Physics and Astronomy, University of Leeds, Leeds, LS2 9JT.
Edited by Peter G. Wolynes, University of California at San Diego, La Jolla, CA, and approved May 12, 2009
Author contributions: S.G.-M. and J.M.F. designed research; S.G.-M., C.L.B., and L.D. performed research; C.B.-F. contributed new reagents/analytic tools; S.G.-M., L.D., and J.M.F. analyzed data; and S.G.-M., L.D., J.B., and J.M.F. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0901213106