PDBsum entry: 1xcg

Signaling protein activator/signaling pr

PDB id: 1xcg

Contents

Protein chains

355 a.a. *

178 a.a. *

Waters ×91

* Residue conservation analysis

PDB id:

1xcg

Name:

Signaling protein activator/signaling pr

Title:

Crystal structure of human rhoa in complex with dh/ph fragment of pdzrhogef

Structure:

Rho guanine nucleotide exchange factor 11. Chain: a, e. Fragment: dh/ph domain. Synonym: pdz-rhogef. Engineered: yes. Transforming protein rhoa. Chain: b, f. Fragment: rhoa. Synonym: h12.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: arhgef11, kiaa0380. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: rhoa, arha, arh12, rho12.

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.235 R-free: 0.281

Authors:

U.Derewenda,A.Oleksy,A.S.Stevenson,J.Korczynska,Z.Dauter, A.P.Somlyo,J.Otlewski,A.V.Somlyo,Z.S.Derewenda

Key ref:

U.Derewenda et al. (2004). 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. PubMed id: 15530360 DOI: 10.1016/j.str.2004.09.003

Date:

01-Sep-04 Release date: 14-Dec-04

Protein chains

O15085  (ARHGB_HUMAN) -  Rho guanine nucleotide exchange factor 11

Seq: 1522 a.a.

Struc: 355 a.a.

Protein chains

P61586  (RHOA_HUMAN) -  Transforming protein RhoA

Seq: 193 a.a.

Struc: 178 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (13 terms)
• Biological process: trabecula morphogenesis (38 terms)
• Biochemical function: protein binding (6 terms)

DOI no: 10.1016/j.str.2004.09.003

Structure 12:1955-1965 (2004)

PubMed id: 15530360

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.

U.Derewenda, A.Oleksy, A.S.Stevenson, J.Korczynska, Z.Dauter, A.P.Somlyo, J.Otlewski, A.V.Somlyo, Z.S.Derewenda.

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.

Selected figure(s)

Figure 3.
Figure 3. The Crystal Structure of the RhoA in Complex with the DH/PH Fragment of PDZRhoGEF and Its Comparison to Complexes with Intersectin and Dbs(A) The general features of the DH-domain (green)-RhoA (yellow) interface, with the PH domain (red) at the rear; the two switch regions of RhoA are shown in purple and labeled; the CR regions of the DH domain are dark green and labeled.(B) A comparable view of the intersectin's DH/PH fragment in complex with Cdc42-1KI1.PDB.(C) A rotated view of the complex shown in A, with the PH domain (red) into the foreground; the unique b4 bulge is shown in turquoise with the dashed line indicating poorly defined fragment, and dark blue indicates the linker region between the DH and PH domains; the DH domain in the background is green.(D) A comparable view of the Dbs DH/PH fragment in complex with RhoA-1LB1.PDB.

The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1955-1965) copyright 2004.

Figure was selected by the author.