2ihb

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the heterodimeric complex of human RGS10 and activated Gi alpha 3

Structural highlights

2ihb is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.71Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.^[1]

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.^[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.

References

↑ Rieder MJ, Green GE, Park SS, Stamper BD, Gordon CT, Johnson JM, Cunniff CM, Smith JD, Emery SB, Lyonnet S, Amiel J, Holder M, Heggie AA, Bamshad MJ, Nickerson DA, Cox TC, Hing AV, Horst JA, Cunningham ML. A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome. Am J Hum Genet. 2012 May 4;90(5):907-14. doi: 10.1016/j.ajhg.2012.04.002. PMID:22560091 doi:10.1016/j.ajhg.2012.04.002
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ihb"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the heterodimeric complex of human RGS10 and activated Gi alpha 3==
-<StructureSection load='2ihb' size='340' side='right' caption='[[2ihb]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
+<StructureSection load='2ihb' size='340' side='right'caption='[[2ihb]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ihb]] is a 2 chain structure with sequence 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=2IHB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IHB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ihb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IHB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IHB FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.71&#8491;</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GNAI3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), RGS10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ihb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ihb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ihb RCSB], [http://www.ebi.ac.uk/pdbsum/2ihb PDBsum]</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=2ihb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ihb OCA], [https://pdbe.org/2ihb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ihb RCSB], [https://www.ebi.ac.uk/pdbsum/2ihb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ihb ProSAT]</span></td></tr>
-<table>
+</table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/GNAI3_HUMAN GNAI3_HUMAN]] Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM:[http://omim.org/entry/602483 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.<ref>PMID:22560091</ref>
+[https://www.uniprot.org/uniprot/GNAI3_HUMAN GNAI3_HUMAN] Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM:[https://omim.org/entry/602483 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.<ref>PMID:22560091</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/GNAI3_HUMAN 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.<ref>PMID:17635935</ref>
+[https://www.uniprot.org/uniprot/GNAI3_HUMAN 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.<ref>PMID:17635935</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ih/2ihb_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ih/2ihb_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ihb ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2ihb" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Guanine nucleotide-binding protein|Guanine nucleotide-binding protein]]
+*[[Regulator of G-protein signaling 3D structures|Regulator of G-protein signaling 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 39: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C.]]
+[[Category: Large Structures]]
-[[Category: Bunkoczi, G.]]
+[[Category: Arrowsmith C]]
-[[Category: Delft, F von.]]
+[[Category: Bunkoczi G]]
-[[Category: Doyle, D A.]]
+[[Category: Doyle DA]]
-[[Category: Edwards, A.]]
+[[Category: Edwards A]]
-[[Category: Gorrec, F.]]
+[[Category: Gorrec F]]
-[[Category: Papagrigoriou, E.]]
+[[Category: Papagrigoriou E]]
-[[Category: Pike, A C.W.]]
+[[Category: Pike ACW]]
-[[Category: SGC, Structural Genomics Consortium.]]
+[[Category: Soundararajan M]]
-[[Category: Soundararajan, M.]]
+[[Category: Sundstrom M]]
-[[Category: Sundstrom, M.]]
+[[Category: Turnbull AP]]
-[[Category: Turnbull, A P.]]
+[[Category: Ugochukwu E]]
-[[Category: Ugochukwu, E.]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J.]]
+[[Category: Von Delft F]]
-[[Category: G protein signalling]]
-[[Category: Heterotrimeric g protein]]
-[[Category: Rg]]
-[[Category: Sgc]]
-[[Category: Signaling protein]]
-[[Category: Signalling complex]]
-[[Category: Structural genomic]]
-[[Category: Structural genomics consortium]]

2ihb

From Proteopedia

Current revision

Crystal structure of the heterodimeric complex of human RGS10 and activated Gi alpha 3

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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