Domain-domain interactions in Filamin A (16-23) impose a hierarchy of unfolding forces

Tianyou Xu, Herbert Lannon, Sébastein Wolf, Fumihiko Nakamura, Jasna Brujic

    Research output: Contribution to journalArticle

    Abstract

    The quaternary structure of Filamin A (FLNa) 16-23 was recently shown to exhibit multiple domain-domain interactions that lead to a propeller-like construction. Here we present single-molecule force spectroscopy experiments to show a wide variety of mechanical responses of this molecule and compare it with its linear counterpart FLNa 1-8. The compact structure of FLNa 16-23 leads to a broad distribution of rupture forces and end-to-end lengths in the force-extension mode and multiple unraveling timescales in the force-clamp mode. Moreover, a subset of force-extension trajectories reveals a mechanical hierarchy in which the rupture of domain-domain interactions at high forces (>200 pN) liberates the unfolding of individual domains at low forces (∼100 pN). This mechanism may also explain the order-of-magnitude difference in the rates of the biexponential fits to the distribution of unfolding dwell times under force-clamp. Overall, FLNa 16-23 under a force of 100 pN is more compliant than the linear FLNa 1-8. Because a physiological role of FLNa is to crosslink actin filaments, this range of responses allows it to accommodate a broad spectrum of forces exerted by the cell and its environment.

    Original languageEnglish (US)
    Pages (from-to)2022-2030
    Number of pages9
    JournalBiophysical Journal
    Volume104
    Issue number9
    DOIs
    StatePublished - May 7 2013

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    Filamins
    Rupture
    Actin Cytoskeleton

    ASJC Scopus subject areas

    • Biophysics

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    Domain-domain interactions in Filamin A (16-23) impose a hierarchy of unfolding forces. / Xu, Tianyou; Lannon, Herbert; Wolf, Sébastein; Nakamura, Fumihiko; Brujic, Jasna.

    In: Biophysical Journal, Vol. 104, No. 9, 07.05.2013, p. 2022-2030.

    Research output: Contribution to journalArticle

    Xu, Tianyou ; Lannon, Herbert ; Wolf, Sébastein ; Nakamura, Fumihiko ; Brujic, Jasna. / Domain-domain interactions in Filamin A (16-23) impose a hierarchy of unfolding forces. In: Biophysical Journal. 2013 ; Vol. 104, No. 9. pp. 2022-2030.
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