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A BAR domain-mediated autoinhibitory mechanism for RhoGAPs of the GRAF family
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2009 (English)In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 417, no 1, 371-377 p.Article in journal (Refereed) Published
Abstract [en]

The BAR (Bin/amphiphysin/Rvs) domain defines an emerging superfamily of proteins implicated in fundamental biological processes by sensing and inducing membrane curvature. We identified a novel autoregulatory function for the BAR domain of two related GAPs' (GTPase-activating proteins) of the GRAF (GTPase regulator associated with focal adhesion kinase) subfamily. We demonstrate that the N-terminal fragment of these GAPs including the BAR domain interacts directly with the GAP domain and inhibits its activity. Analysis of various BAR and GAP domains revealed that the BAR domain-mediated inhibition of these GAPs' function is highly specific. These GAPs, in their autoinhibited state, are able to bind and tubulate liposomes in vitro, and to generate lipid tubules in cells. Taken together, we identified BAR domains as cis-acting inhibitory elements that very likely mask the active sites of the GAP domains and thus prevent down-regulation of Rho proteins. Most remarkably, these BAR proteins represent a dual-site system with separate membrane-tubulation and GAP-inhibitory functions that operate simultaneously.

Place, publisher, year, edition, pages
2009. Vol. 417, no 1, 371-377 p.
Keyword [en]
autoregulation, autoinhibited state, Bin/amphiphysin/Rvs (BAR) domain, GTPase-activating protein (GAP), GTP hydrolysis, GTPase reaction, Rho protein family
URN: urn:nbn:se:umu:diva-42777DOI: 10.1042/BJ20081535PubMedID: 18954304OAI: diva2:410369
Available from: 2011-04-13 Created: 2011-04-13 Last updated: 2011-04-13Bibliographically approved

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Lundmark, Richard
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