2ode

Crystal structure of the heterodimeric complex of human RGS8 and activated Gi alpha 3

spinqualitylabelsall models 2ode, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ode is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ALF, GDP, MG Gene: GNAI3 (HUMAN), RGS8 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [GNAI3_HUMAN] Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM:602483]. ARCND1 is an autosomal dominant craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia. Function [GNAI3_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(k) is the stimulatory G protein of receptor-regulated K(+) channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division. [RGS8_HUMAN] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Preferentially binds to G(o)-alpha and G(i)-alpha-3 (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Galpha subunits and thus facilitate termination of signaling initiated by G protein-coupled receptors (GPCRs). RGS proteins hold great promise as disease intervention points, given their signature role as negative regulators of GPCRs-receptors to which the largest fraction of approved medications are currently directed. RGS proteins share a hallmark RGS domain that interacts most avidly with Galpha when in its transition state for GTP hydrolysis; by binding and stabilizing switch regions I and II of Galpha, RGS domain binding consequently accelerates Galpha-mediated GTP hydrolysis. The human genome encodes more than three dozen RGS domain-containing proteins with varied Galpha substrate specificities. To facilitate their exploitation as drug-discovery targets, we have taken a systematic structural biology approach toward cataloging the structural diversity present among RGS domains and identifying molecular determinants of their differential Galpha selectivities. Here, we determined 14 structures derived from NMR and x-ray crystallography of members of the R4, R7, R12, and RZ subfamilies of RGS proteins, including 10 uncomplexed RGS domains and 4 RGS domain/Galpha complexes. Heterogeneity observed in the structural architecture of the RGS domain, as well as in engagement of switch III and the all-helical domain of the Galpha substrate, suggests that unique structural determinants specific to particular RGS protein/Galpha pairings exist and could be used to achieve selective inhibition by small molecules. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits.,Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA, Hutsell SQ, Sundstrom M, Doyle DA, Siderovski DP Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6457-62. Epub 2008 Apr 23. PMID:18434541 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Guanine nucleotide-binding protein

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