5my3 | pdb_00005my3
Crystal structure of the RhoGAP domain of Rgd1p at 2.19 Angstroms resolution
Structural highlights
FunctionRGD1_YEAST GTPase activating protein of RHO3 and RHO4. Acts in concert with MID2 in cell integrity, which is functionally linked to the PKC pathway. Involved in various stress responses. Required at low pH for activation of the PKC pathway. Important during mating response.[1] [2] [3] [4] [5] Publication Abstract from PubMedPhosphoinositide lipids recruit proteins to the plasma membrane involved in the regulation of cytoskeleton organization and in signalling pathways that control cell polarity and growth. Among those, Rgd1p is a yeast GTPase-activating protein (GAP) specific for Rho3p and Rho4p GTPases, which control actin polymerization and stress signalling pathways. Phosphoinositides not only bind Rgd1p, but also stimulate its GAP activity on the membrane-anchored form of Rho4p. Both F-BAR (F-BAR FCH, and BAR) and RhoGAP domains of Rgd1p are involved in lipid interactions. In the Rgd1p-F-BAR domain, a phosphoinositide-binding site has been recently characterized. We report here the X-ray structure of the Rgd1p-RhoGAP domain, identify by NMR spectroscopy and confirm by docking simulations, a new but cryptic phosphoinositide-binding site, comprising contiguous A1, A1' and B helices. The addition of helix A1', unusual among RhoGAP domains, seems to be crucial for lipid interactions. Such a site was totally unexpected inside a RhoGAP domain, as it was not predicted from either the protein sequence or its three-dimensional structure. Phosphoinositide-binding sites in RhoGAP domains have been reported to correspond to polybasic regions, which are located at the unstructured flexible termini of proteins. Solid-state NMR spectroscopy experiments confirm the membrane interaction of the Rgd1p-RhoGAP domain upon the addition of PtdIns(4,5)P2 and indicate a slight membrane destabilization in the presence of the two partners. Structural evidence of a phosphoinositide-binding site in the Rgd1-RhoGAP domain.,Martinez D, Langlois d'Estaintot B, Granier T, Tolchard J, Courreges C, Prouzet-Mauleon V, Hugues M, Gallois B, Doignon F, Odaert B Biochem J. 2017 Sep 20;474(19):3307-3319. doi: 10.1042/BCJ20170331. PMID:28760887[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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