1A2B

HUMAN RHOA COMPLEXED WITH GTP ANALOGUE

1A2B の概要

• エントリーDOI: 10.2210/pdb1a2b/pdb
• 分子名称: TRANSFORMING PROTEIN RHOA, MAGNESIUM ION, 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: small g-protein, signal transduction, gtpase, ras superfamily, oncogene protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side: P61586
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21160.17

構造登録者

Ihara, K.,Muraguchi, S.,Kato, M.,Shimizu, T.,Shirakawa, M.,Kuroda, S.,Kaibuchi, K.,Hakoshima, T. (登録日: 1997-12-26, 公開日: 1998-06-17, 最終更新日: 2024-05-22)

主引用文献

Ihara, K.,Muraguchi, S.,Kato, M.,Shimizu, T.,Shirakawa, M.,Kuroda, S.,Kaibuchi, K.,Hakoshima, T.
Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogue.
J.Biol.Chem., 273:9656-9666, 1998

PubMed Abstract: The 2.4-A resolution crystal structure of a dominantly active form of the small guanosine triphosphatase (GTPase) RhoA, RhoAV14, complexed with the nonhydrolyzable GTP analogue, guanosine 5'-3-O-(thio)triphosphate (GTPgammaS), reveals a fold similar to RhoA-GDP, which has been recently reported (Wei, Y., Zhang, Y., Derewenda, U., Liu, X., Minor, W., Nakamoto, R. K., Somlyo, A. V., Somlyo, A. P., and Derewenda, Z. S. (1997) Nat. Struct. Biol. 4, 699-703), but shows large conformational differences localized in switch I and switch II. These changes produce hydrophobic patches on the molecular surface of switch I, which has been suggested to be involved in its effector binding. Compared with H-Ras and other GTPases bound to GTP or GTP analogues, the significant conformational differences are located in regions involving switches I and II and part of the antiparallel beta-sheet between switches I and II. Key residues that produce these conformational differences were identified. In addition to these differences, RhoA contains four insertion or deletion sites with an extra helical subdomain that seems to be characteristic of members of the Rho family, including Rac1, but with several variations in details. These sites also display large displacements from those of H-Ras. The ADP-ribosylation residue, Asn41, by C3-like exoenzymes stacks on the indole ring of Trp58 with a hydrogen bond to the main chain of Glu40. The recognition of the guanosine moiety of GTPgammaS by the GTPase contains water-mediated hydrogen bonds, which seem to be common in the Rho family. These structural differences provide an insight into specific interaction sites with the effectors, as well as with modulators such as guanine nucleotide exchange factor (GEF) and guanine nucleotide dissociation inhibitor (GDI).

PubMed: 9545299
DOI: 10.1074/jbc.273.16.9656

実験手法

X-RAY DIFFRACTION (2.4 Å)