| Structural highlights
Function
[RGD1_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 PubMed
Phosphoinositide 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.
References
- ↑ Doignon F, Weinachter C, Roumanie O, Crouzet M. The yeast Rgd1p is a GTPase activating protein of the Rho3 and rho4 proteins. FEBS Lett. 1999 Oct 15;459(3):458-62. PMID:10526184
- ↑ de Bettignies G, Barthe C, Morel C, Peypouquet MF, Doignon F, Crouzet M. RGD1 genetically interacts with MID2 and SLG1, encoding two putative sensors for cell integrity signalling in Saccharomyces cerevisiae. Yeast. 1999 Dec;15(16):1719-31. PMID:10590461 doi:<1719::AID-YEA499>3.0.CO;2-F http://dx.doi.org/10.1002/(SICI)1097-0061(199912)15:16<1719::AID-YEA499>3.0.CO;2-F
- ↑ de Bettignies G, Thoraval D, Morel C, Peypouquet MF, Crouzet M. Overactivation of the protein kinase C-signaling pathway suppresses the defects of cells lacking the Rho3/Rho4-GAP Rgd1p in Saccharomyces cerevisiae. Genetics. 2001 Dec;159(4):1435-48. PMID:11779787
- ↑ Gatti X, de Bettignies G, Claret S, Doignon F, Crouzet M, Thoraval D. RGD1, encoding a RhoGAP involved in low-pH survival, is an Msn2p/Msn4p regulated gene in Saccharomyces cerevisiae. Gene. 2005 May 23;351:159-69. PMID:15922872 doi:http://dx.doi.org/10.1016/j.gene.2005.03.034
- ↑ Claret S, Gatti X, Doignon F, Thoraval D, Crouzet M. The Rgd1p Rho GTPase-activating protein and the Mid2p cell wall sensor are required at low pH for protein kinase C pathway activation and cell survival in Saccharomyces cerevisiae. Eukaryot Cell. 2005 Aug;4(8):1375-86. PMID:16087742 doi:http://dx.doi.org/10.1128/EC.4.8.1375-1386.2005
- ↑ Martinez D, Langlois d'Estaintot B, Granier T, Tolchard J, Courreges C, Prouzet-Mauleon V, Hugues M, Gallois B, Doignon F, Odaert B. Structural evidence of a phosphoinositide-binding site in the Rgd1-RhoGAP domain. Biochem J. 2017 Sep 20;474(19):3307-3319. doi: 10.1042/BCJ20170331. PMID:28760887 doi:http://dx.doi.org/10.1042/BCJ20170331
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