1XCG

Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF

1XCG の概要

• エントリーDOI: 10.2210/pdb1xcg/pdb
• 分子名称: Rho guanine nucleotide exchange factor 11, Transforming protein RhoA (3 entities in total)
• 機能のキーワード: x-ray crystallography; regulation of rhoa gtpase; protein complex, signaling protein activator-signaling protein complex, signaling protein activator/signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: O15085; Cell membrane; Lipid-anchor; Cytoplasmic side: P61586
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 125875.00

構造登録者

Derewenda, U.,Oleksy, A.,Stevenson, A.S.,Korczynska, J.,Dauter, Z.,Somlyo, A.P.,Otlewski, J.,Somlyo, A.V.,Derewenda, Z.S. (登録日: 2004-09-01, 公開日: 2004-12-14, 最終更新日: 2024-02-14)

主引用文献

Derewenda, U.,Oleksy, A.,Stevenson, A.S.,Korczynska, J.,Dauter, Z.,Somlyo, A.P.,Otlewski, J.,Somlyo, A.V.,Derewenda, Z.S.
The crystal structure of RhoA in complex with the DH/PH fragment of PDZRhoGEF, an activator of the Ca(2+) sensitization pathway in smooth muscle
Structure, 12:1955-1965, 2004

PubMed Abstract: Calcium sensitization in smooth muscle is mediated by the RhoA GTPase, activated by hitherto unspecified nucleotide exchange factors (GEFs) acting downstream of Galphaq/Galpha(12/13) trimeric G proteins. Here, we show that at least one potential GEF, the PDZRhoGEF, is present in smooth muscle, and its isolated DH/PH fragment induces calcium sensitization in the absence of agonist-mediated signaling. In vitro, the fragment shows high selectivity for the RhoA GTPase. Full-length fragment is required for the nucleotide exchange, as the isolated DH domain enhances it only marginally. We crystallized the DH/PH fragment of PDZRhoGEF in complex with nonprenylated human RhoA and determined the structure at 2.5 A resolution. The refined molecular model reveals that the mutual disposition of the DH and PH domains is significantly different from other previously described complexes involving DH/PH tandems, and that the PH domain interacts with RhoA in a unique mode. The DH domain makes several specific interactions with RhoA residues not conserved among other Rho family members, suggesting the molecular basis for the observed specificity.

PubMed: 15530360
DOI: 10.1016/j.str.2004.09.003

実験手法

X-RAY DIFFRACTION (2.5 Å)