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| | ==Solution structure of the RGS domain of human RGS14== | | ==Solution structure of the RGS domain of human RGS14== |
| - | <StructureSection load='2jnu' size='340' side='right'caption='[[2jnu]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2jnu' size='340' side='right'caption='[[2jnu]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jnu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JNU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jnu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JNU FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RGS14 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jnu OCA], [https://pdbe.org/2jnu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jnu RCSB], [https://www.ebi.ac.uk/pdbsum/2jnu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jnu ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jnu OCA], [https://pdbe.org/2jnu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jnu RCSB], [https://www.ebi.ac.uk/pdbsum/2jnu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jnu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RGS14_HUMAN RGS14_HUMAN]] Acts as a regulator of G protein signaling (RGS). Modulates G protein alpha subunits nucleotide exchange and hydrolysis activities by functioning either as a GTPase-activating protein (GAP), thereby driving G protein alpha subunits into their inactive GDP-bound form, or as a GDP-dissociation inhibitor (GDI). Confers GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not G(o) alpha subunit GNAO1 and G(i) alpha subunit GNAI2. Confers GAP activity on G(o) alpha subunit GNAI0 and G(i) alpha subunits GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS1 and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Probably required for the nerve growth factor (NGF)-mediated neurite outgrowth. May be involved in visual memory processing capacity and hippocampal-based learning and memory.<ref>PMID:15917656</ref> <ref>PMID:17635935</ref>
| + | [https://www.uniprot.org/uniprot/RGS14_HUMAN RGS14_HUMAN] Acts as a regulator of G protein signaling (RGS). Modulates G protein alpha subunits nucleotide exchange and hydrolysis activities by functioning either as a GTPase-activating protein (GAP), thereby driving G protein alpha subunits into their inactive GDP-bound form, or as a GDP-dissociation inhibitor (GDI). Confers GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not G(o) alpha subunit GNAO1 and G(i) alpha subunit GNAI2. Confers GAP activity on G(o) alpha subunit GNAI0 and G(i) alpha subunits GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS1 and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Probably required for the nerve growth factor (NGF)-mediated neurite outgrowth. May be involved in visual memory processing capacity and hippocampal-based learning and memory.<ref>PMID:15917656</ref> <ref>PMID:17635935</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C]] | + | [[Category: Arrowsmith C]] |
| - | [[Category: Ball, L J]] | + | [[Category: Ball LJ]] |
| - | [[Category: Bray, J]] | + | [[Category: Bray J]] |
| - | [[Category: Brockmann, C]] | + | [[Category: Brockmann C]] |
| - | [[Category: Diehl, A]] | + | [[Category: Diehl A]] |
| - | [[Category: Dowler, E F]] | + | [[Category: Dowler EF]] |
| - | [[Category: Doyle, D A]] | + | [[Category: Doyle DA]] |
| - | [[Category: Edwards, A]] | + | [[Category: Edwards A]] |
| - | [[Category: Elkins, J]] | + | [[Category: Elkins J]] |
| - | [[Category: Gileadi, C]] | + | [[Category: Gileadi C]] |
| - | [[Category: Higman, V A]] | + | [[Category: Higman VA]] |
| - | [[Category: Kuhne, R]] | + | [[Category: Kuhne R]] |
| - | [[Category: Leidert, M]] | + | [[Category: Leidert M]] |
| - | [[Category: Oschkinat, H]] | + | [[Category: Oschkinat H]] |
| - | [[Category: Phillips, C]] | + | [[Category: Phillips C]] |
| - | [[Category: Rehbein, K]] | + | [[Category: Rehbein K]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Schmieder P]] |
| - | [[Category: Schmieder, P]] | + | [[Category: Schoch GA]] |
| - | [[Category: Schoch, G A]] | + | [[Category: Soundararajan M]] |
| - | [[Category: Soundararajan, M]] | + | [[Category: Sundstrom M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Yang X]] |
| - | [[Category: Yang, X]] | + | |
| - | [[Category: Regulator of g-protein signalling domain]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
RGS14_HUMAN Acts as a regulator of G protein signaling (RGS). Modulates G protein alpha subunits nucleotide exchange and hydrolysis activities by functioning either as a GTPase-activating protein (GAP), thereby driving G protein alpha subunits into their inactive GDP-bound form, or as a GDP-dissociation inhibitor (GDI). Confers GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not G(o) alpha subunit GNAO1 and G(i) alpha subunit GNAI2. Confers GAP activity on G(o) alpha subunit GNAI0 and G(i) alpha subunits GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS1 and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Probably required for the nerve growth factor (NGF)-mediated neurite outgrowth. May be involved in visual memory processing capacity and hippocampal-based learning and memory.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martin-McCaffrey L, Willard FS, Pajak A, Dagnino L, Siderovski DP, D'Souza SJ. RGS14 is a microtubule-associated protein. Cell Cycle. 2005 Jul;4(7):953-60. Epub 2005 Jul 28. PMID:15917656
- ↑ Cho H, Kehrl JH. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. PMID:17635935 doi:10.1083/jcb.200604114
- ↑ 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. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6457-62. Epub 2008 Apr 23. PMID:18434541
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