A BAR domain-mediated autoinhibitory mechanism for RhoGAPs of the GRAF family

Tyck till om SwePub Sök här!

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.

Lundmark, RichardUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)rilu0004 (författare)
Gremer, Lothar (författare)
Dvorsky, Radovan (författare)
Koessmeier, Katja T (författare)
McMahon, Harvey T (författare)
Ahmadian, Mohammad Reza (författare)
Umeå universitetInstitutionen för medicinsk kemi och biofysik (creator_code:org_t)

Av författaren/redakt...: Eberth, Alexande ...; Lundmark, Richar ...; Gremer, Lothar; Dvorsky, Radovan; Koessmeier, Katj ...; McMahon, Harvey ...; visa fler...; Ahmadian, Mohamm ...; visa färre...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.