4wpc

Crystal structure of Rgd1p F-BAR domain in complex with inositol phosphateCrystal structure of Rgd1p F-BAR domain in complex with inositol phosphate

Structural highlights

4wpc is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.34Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although they are generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the Saccharomyces cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity and provide a basis for its prediction from sequence.

Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site.,Moravcevic K, Alvarado D, Schmitz KR, Kenniston JA, Mendrola JM, Ferguson KM, Lemmon MA Structure. 2015 Feb 3;23(2):352-63. doi: 10.1016/j.str.2014.12.009. Epub 2015 Jan, 22. PMID:25620000^[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
↑ Moravcevic K, Alvarado D, Schmitz KR, Kenniston JA, Mendrola JM, Ferguson KM, Lemmon MA. Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site. Structure. 2015 Feb 3;23(2):352-63. doi: 10.1016/j.str.2014.12.009. Epub 2015 Jan, 22. PMID:25620000 doi:http://dx.doi.org/10.1016/j.str.2014.12.009

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OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] Moravcevic K, Alvarado D, Schmitz KR, Kenniston JA, Mendrola JM, Ferguson KM, Lemmon MA. Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site. Structure. 2015 Feb 3;23(2):352-63. doi: 10.1016/j.str.2014.12.009. Epub 2015 Jan, 22. PMID:25620000 doi:http://dx.doi.org/10.1016/j.str.2014.12.009

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