3REG

Crystal structure of EhRho1 bound to a GTP analog and Magnesium

3REG の概要

• エントリーDOI: 10.2210/pdb3reg/pdb
• 関連するPDBエントリー: 1A2B 3REF
• 分子名称: Rho-like small GTPase, 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: cytoskeleton, nucleotide-binding, gtp-binding, signaling protein, lipoprotein, prenylation
• 由来する生物種: Entamoeba histolytica
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43992.01

構造登録者

Bosch, D.E.,Qiu, C.,Siderovski, D.P. (登録日: 2011-04-04, 公開日: 2011-09-28, 最終更新日: 2023-09-13)

主引用文献

Bosch, D.E.,Wittchen, E.S.,Qiu, C.,Burridge, K.,Siderovski, D.P.
Unique structural and nucleotide exchange features of the Rho1 GTPase of Entamoeba histolytica.
J.Biol.Chem., 286:39236-39246, 2011

PubMed Abstract: The single-celled human parasite Entamoeba histolytica possesses a dynamic actin cytoskeleton vital for its intestinal and systemic pathogenicity. The E. histolytica genome encodes several Rho family GTPases known to regulate cytoskeletal dynamics. EhRho1, the first family member identified, was reported to be insensitive to the Rho GTPase-specific Clostridium botulinum C3 exoenzyme, raising the possibility that it may be a misclassified Ras family member. Here, we report the crystal structures of EhRho1 in both active and inactive states. EhRho1 is activated by a conserved switch mechanism, but diverges from mammalian Rho GTPases in lacking a signature Rho insert helix. EhRho1 engages a homolog of mDia, EhFormin1, suggesting a role in mediating serum-stimulated actin reorganization and microtubule formation during mitosis. EhRho1, but not a constitutively active mutant, interacts with a newly identified EhRhoGDI in a prenylation-dependent manner. Furthermore, constitutively active EhRho1 induces actin stress fiber formation in mammalian fibroblasts, thereby identifying it as a functional Rho family GTPase. EhRho1 exhibits a fast rate of nucleotide exchange relative to mammalian Rho GTPases due to a distinctive switch one isoleucine residue reminiscent of the constitutively active F28L mutation in human Cdc42, which for the latter protein, is sufficient for cellular transformation. Nonconserved, nucleotide-interacting residues within EhRho1, revealed by the crystal structure models, were observed to contribute a moderating influence on fast spontaneous nucleotide exchange. Collectively, these observations indicate that EhRho1 is a bona fide member of the Rho GTPase family, albeit with unique structural and functional aspects compared with mammalian Rho GTPases.

PubMed: 21930699
DOI: 10.1074/jbc.M111.253898

実験手法

X-RAY DIFFRACTION (1.801 Å)