2R09

Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor

2R09 の概要

• エントリーDOI: 10.2210/pdb2r09/pdb
• 関連するPDBエントリー: 2r0d
• 分子名称: Cytohesin-3, SULFATE ION, INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: autoinhibition, grp1, pip3, arf, 3-phosphoinositide, pleckstrin homology domain, guanine-nucleotide releasing factor, signaling protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cell membrane (By similarity): O08967
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83897.29

構造登録者

DiNitto, J.P.,Delprato, A.,Gabe Lee, M.T.,Cronin, T.C.,Huang, S.,Guilherme, A.,Czech, M.P.,Lambright, D.G. (登録日: 2007-08-17, 公開日: 2007-12-04, 最終更新日: 2024-10-30)

主引用文献

DiNitto, J.P.,Delprato, A.,Gabe Lee, M.T.,Cronin, T.C.,Huang, S.,Guilherme, A.,Czech, M.P.,Lambright, D.G.
Structural Basis and Mechanism of Autoregulation in 3-Phosphoinositide-Dependent Grp1 Family Arf GTPase Exchange Factors.
Mol.Cell, 28:569-583, 2007

PubMed Abstract: 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.

PubMed: 18042453
DOI: 10.1016/j.molcel.2007.09.017

実験手法

X-RAY DIFFRACTION (1.9 Å)