1XCG
Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF
Summary for 1XCG
| Entry DOI | 10.2210/pdb1xcg/pdb |
| Descriptor | Rho guanine nucleotide exchange factor 11, Transforming protein RhoA (3 entities in total) |
| Functional Keywords | x-ray crystallography; regulation of rhoa gtpase; protein complex, signaling protein activator-signaling protein complex, signaling protein activator/signaling protein |
| Biological source | Homo sapiens (human) More |
| Cellular location | Cytoplasm: O15085 Cell membrane; Lipid-anchor; Cytoplasmic side: P61586 |
| Total number of polymer chains | 4 |
| Total formula weight | 125875.00 |
| Authors | Derewenda, U.,Oleksy, A.,Stevenson, A.S.,Korczynska, J.,Dauter, Z.,Somlyo, A.P.,Otlewski, J.,Somlyo, A.V.,Derewenda, Z.S. (deposition date: 2004-09-01, release date: 2004-12-14, Last modification date: 2024-02-14) |
| Primary citation | 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 Cited by 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: 15530360DOI: 10.1016/j.str.2004.09.003 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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