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

Sergi Garcia-Manyes, Lorna Dougan, Carmen L. Badilla, Jasna Brujić, Julio M. Fernández

    Research output: Contribution to journalArticle

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)10534-10539
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume106
    Issue number26
    DOIs
    StatePublished - Jun 30 2009

    Fingerprint

    Ubiquitin
    Observation
    Proteins
    Protein Folding
    Statistical Models
    Mechanics
    Reproducibility of Results
    Spectrum Analysis

    Keywords

    • Force-clamp spectroscopy
    • Protein folding

    ASJC Scopus subject areas

    • General

    Cite this

    Direct observation of an ensemble of stable collapsed states in the mechanical folding of ubiquitin. / Garcia-Manyes, Sergi; Dougan, Lorna; Badilla, Carmen L.; Brujić, Jasna; Fernández, Julio M.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 26, 30.06.2009, p. 10534-10539.

    Research output: Contribution to journalArticle

    Garcia-Manyes, Sergi ; Dougan, Lorna ; Badilla, Carmen L. ; Brujić, Jasna ; Fernández, Julio M. / Direct observation of an ensemble of stable collapsed states in the mechanical folding of ubiquitin. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 26. pp. 10534-10539.
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