2r09
From Proteopedia
(New page: 200px<br /><applet load="2r09" size="350" color="white" frame="true" align="right" spinBox="true" caption="2r09, resolution 1.90Å" /> '''Crystal Structure of...) |
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==Overview== | ==Overview== | ||
| - | Arf GTPases regulate membrane trafficking and actin dynamics. Grp1, ARNO, and Cytohesin-1 comprise a family of phosphoinositide-dependent Arf GTPase | + | Arf GTPases regulate membrane trafficking and actin dynamics. Grp1, ARNO, and Cytohesin-1 comprise a family of phosphoinositide-dependent Arf GTPase exchange factors with a Sec7-pleckstrin homology (PH) domain tandem. Here, we report that the exchange activity of the Sec7 domain is potently autoinhibited by conserved elements proximal to the PH domain. The crystal structure of the Grp1 Sec7-PH tandem reveals a pseudosubstrate mechanism of autoinhibition in which the linker region between domains and a C-terminal amphipathic helix physically block the docking sites for the switch regions of Arf GTPases. Mutations within either element result in partial or complete activation. Critical determinants of autoinhibition also contribute to insulin-stimulated plasma membrane recruitment. Autoinhibition can be largely reversed by binding of active Arf6 to Grp1 and by phosphorylation of tandem PKC sites in Cytohesin-1. These observations suggest that Grp1 family GEFs are autoregulated by mechanisms that depend on plasma membrane recruitment for activation. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Structural | + | Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors., DiNitto JP, Delprato A, Gabe Lee MT, Cronin TC, Huang S, Guilherme A, Czech MP, Lambright DG, Mol Cell. 2007 Nov 30;28(4):569-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18042453 18042453] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cronin, T | + | [[Category: Cronin, T C.]] |
| - | [[Category: Czech, M | + | [[Category: Czech, M P.]] |
[[Category: Delprato, A.]] | [[Category: Delprato, A.]] | ||
| - | [[Category: Dinitto, J | + | [[Category: Dinitto, J P.]] |
[[Category: Guilherme, A.]] | [[Category: Guilherme, A.]] | ||
[[Category: Huang, S.]] | [[Category: Huang, S.]] | ||
| - | [[Category: Lambright, D | + | [[Category: Lambright, D G.]] |
| - | [[Category: Lee, M | + | [[Category: Lee, M T.Gabe.]] |
[[Category: 4IP]] | [[Category: 4IP]] | ||
[[Category: PE5]] | [[Category: PE5]] | ||
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[[Category: signaling protein]] | [[Category: signaling protein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:43:41 2008'' |
Revision as of 16:43, 21 February 2008
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Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor
Overview
Arf GTPases regulate membrane trafficking and actin dynamics. Grp1, ARNO, and Cytohesin-1 comprise a family of phosphoinositide-dependent Arf GTPase exchange factors with a Sec7-pleckstrin homology (PH) domain tandem. Here, we report that the exchange activity of the Sec7 domain is potently autoinhibited by conserved elements proximal to the PH domain. The crystal structure of the Grp1 Sec7-PH tandem reveals a pseudosubstrate mechanism of autoinhibition in which the linker region between domains and a C-terminal amphipathic helix physically block the docking sites for the switch regions of Arf GTPases. Mutations within either element result in partial or complete activation. Critical determinants of autoinhibition also contribute to insulin-stimulated plasma membrane recruitment. Autoinhibition can be largely reversed by binding of active Arf6 to Grp1 and by phosphorylation of tandem PKC sites in Cytohesin-1. These observations suggest that Grp1 family GEFs are autoregulated by mechanisms that depend on plasma membrane recruitment for activation.
About this Structure
2R09 is a Single protein structure of sequence from Mus musculus with , , and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors., DiNitto JP, Delprato A, Gabe Lee MT, Cronin TC, Huang S, Guilherme A, Czech MP, Lambright DG, Mol Cell. 2007 Nov 30;28(4):569-83. PMID:18042453
Page seeded by OCA on Thu Feb 21 18:43:41 2008
Categories: Mus musculus | Single protein | Cronin, T C. | Czech, M P. | Delprato, A. | Dinitto, J P. | Guilherme, A. | Huang, S. | Lambright, D G. | Lee, M T.Gabe. | 4IP | PE5 | PGE | SO4 | 3-phosphoinositide | Arf | Autoinhibition | Coiled coil | Grp1 | Guanine-nucleotide releasing factor | Pip3 | Pleckstrin homology domain | Signaling protein
