1xcg
From Proteopedia
(New page: 200px<br /> <applet load="1xcg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xcg, resolution 2.50Å" /> '''Crystal Structure o...) |
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| - | [[Image:1xcg.gif|left|200px]]<br /> | + | [[Image:1xcg.gif|left|200px]]<br /><applet load="1xcg" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xcg" size=" | + | |
caption="1xcg, resolution 2.50Å" /> | caption="1xcg, resolution 2.50Å" /> | ||
'''Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF'''<br /> | '''Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Calcium sensitization in smooth muscle is mediated by the RhoA GTPase, activated by hitherto unspecified nucleotide exchange factors (GEFs) | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1XCG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1XCG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XCG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Dauter, Z.]] | [[Category: Dauter, Z.]] | ||
[[Category: Derewenda, U.]] | [[Category: Derewenda, U.]] | ||
| - | [[Category: Derewenda, Z | + | [[Category: Derewenda, Z S.]] |
[[Category: Korczynska, J.]] | [[Category: Korczynska, J.]] | ||
[[Category: Oleksy, A.]] | [[Category: Oleksy, A.]] | ||
[[Category: Otlewski, J.]] | [[Category: Otlewski, J.]] | ||
| - | [[Category: Somlyo, A | + | [[Category: Somlyo, A P.]] |
| - | [[Category: Somlyo, A | + | [[Category: Somlyo, A V.]] |
| - | [[Category: Stevenson, A | + | [[Category: Stevenson, A S.]] |
[[Category: x-ray crystallography; regulation of rhoa gtpase; protein complex]] | [[Category: x-ray crystallography; regulation of rhoa gtpase; protein complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:17 2008'' |
Revision as of 13:53, 21 February 2008
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Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF
Overview
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.
About this Structure
1XCG is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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., Derewenda U, Oleksy A, Stevenson AS, Korczynska J, Dauter Z, Somlyo AP, Otlewski J, Somlyo AV, Derewenda ZS, Structure. 2004 Nov;12(11):1955-65. PMID:15530360
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