BIROn - Birkbeck Institutional Research Online

    ATP-triggered conformational changes delineate substrate-binding and -folding mechanics of the GroEL Chaperonin

    Clare, Daniel K. and Vasishtan, Daven and Stagg, S. and Quispe, J. and Farr, G.W. and Topf, Maya and Horwich, A.L. and Saibil, Helen R. (2012) ATP-triggered conformational changes delineate substrate-binding and -folding mechanics of the GroEL Chaperonin. Cell 149 (1), pp. 113-123. ISSN 0092-8674.

    Full text not available from this repository.

    Abstract

    The chaperonin GroEL assists the folding of nascent or stress-denatured polypeptides by actions of binding and encapsulation. ATP binding initiates a series of conformational changes triggering the association of the cochaperonin GroES, followed by further large movements that eject the substrate polypeptide from hydrophobic binding sites into a GroES-capped, hydrophilic folding chamber. We used cryo-electron microscopy, statistical analysis, and flexible fitting to resolve a set of distinct GroEL-ATP conformations that can be ordered into a trajectory of domain rotation and elevation. The initial conformations are likely to be the ones that capture polypeptide substrate. Then the binding domains extend radially to separate from each other but maintain their binding surfaces facing the cavity, potentially exerting mechanical force upon kinetically trapped, misfolded substrates. The extended conformation also provides a potential docking site for GroES, to trigger the final, 100° domain rotation constituting the “power stroke” that ejects substrate into the folding chamber.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Bioinformatics, Bloomsbury Centre for, Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 23 Mar 2012 09:40
    Last Modified: 07 Dec 2016 15:02
    URI: http://eprints.bbk.ac.uk/id/eprint/4660

    Statistics

    Downloads
    Activity Overview
    0Downloads
    591Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item