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2acx

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Crystal Structure of G protein coupled receptor kinase 6 bound to AMPPNP

Structural highlights

2acx 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 2.6Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GRK6_HUMAN Specifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (By similarity). Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor: LRP6 during Wnt signaling (in vitro).^[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

We describe the 2.6-A crystal structure of human G protein-coupled receptor kinase (GRK)-6, a key regulator of dopaminergic signaling and lymphocyte chemotaxis. GRK6 is a member of the GRK4 subfamily of GRKs, which is represented in most, if not all, metazoans. Comparison of GRK6 with GRK2 confirms that the catalytic core of all GRKs consists of intimately associated kinase and regulator of G protein signaling (RGS) homology domains. Despite being in complex with an ATP analog, the kinase domain of GRK6 remains in an open, presumably inactive conformation, suggesting that G protein-coupled receptors activate GRKs by inducing kinase domain closure. The structure reveals a putative phospholipid-binding site near the N terminus of GRK6 and structural elements within the kinase substrate channel that likely influence G protein-coupled receptor access and specificity. The crystalline GRK6 RGS homology domain forms an extensive dimer interface using conserved hydrophobic residues distinct from those in GRK2 that bind Galpha(q), although dimerization does not appear to occur in solution and is not required for receptor phosphorylation.

The structure of G protein-coupled receptor kinase (GRK)-6 defines a second lineage of GRKs.,Lodowski DT, Tesmer VM, Benovic JL, Tesmer JJ J Biol Chem. 2006 Jun 16;281(24):16785-93. Epub 2006 Apr 13. PMID:16613860^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chen M, Philipp M, Wang J, Premont RT, Garrison TR, Caron MG, Lefkowitz RJ, Chen W. G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway. J Biol Chem. 2009 Dec 11;284(50):35040-8. doi: 10.1074/jbc.M109.047456. Epub 2009, Oct 2. PMID:19801552 doi:10.1074/jbc.M109.047456
↑ Busillo JM, Armando S, Sengupta R, Meucci O, Bouvier M, Benovic JL. Site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases and results in differential modulation of CXCR4 signaling. J Biol Chem. 2010 Mar 5;285(10):7805-17. doi: 10.1074/jbc.M109.091173. Epub 2010 , Jan 4. PMID:20048153 doi:10.1074/jbc.M109.091173
↑ Lodowski DT, Tesmer VM, Benovic JL, Tesmer JJ. The structure of G protein-coupled receptor kinase (GRK)-6 defines a second lineage of GRKs. J Biol Chem. 2006 Jun 16;281(24):16785-93. Epub 2006 Apr 13. PMID:16613860 doi:10.1074/jbc.M601327200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Crystal Structure of G protein coupled receptor kinase 6 bound to AMPPNP==
-<StructureSection load='2acx' size='340' side='right' caption='[[2acx]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+<StructureSection load='2acx' size='340' side='right'caption='[[2acx]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2acx]] 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=2ACX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ACX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2acx]] 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=2ACX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ACX FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.6&#8491;</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRK6, GPRK6 ([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=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=2acx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2acx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2acx RCSB], [http://www.ebi.ac.uk/pdbsum/2acx 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=2acx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2acx OCA], [https://pdbe.org/2acx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2acx RCSB], [https://www.ebi.ac.uk/pdbsum/2acx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2acx ProSAT]</span></td></tr>
-<table>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/GRK6_HUMAN GRK6_HUMAN] Specifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (By similarity). Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor: LRP6 during Wnt signaling (in vitro).<ref>PMID:19801552</ref> <ref>PMID:20048153</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/ac/2acx_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ac/2acx_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=2acx ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2acx" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 30: / Line 34: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Benovic, J L.]]
+[[Category: Large Structures]]
-[[Category: Lodowski, D T.]]
+[[Category: Benovic JL]]
-[[Category: Tesmer, J J.]]
+[[Category: Lodowski DT]]
-[[Category: Tesmer, V M.]]
+[[Category: Tesmer JJ]]
-[[Category: G protein]]
+[[Category: Tesmer VM]]
-[[Category: G protein coupled receptor kinase]]
-[[Category: Grk]]
-[[Category: Grk6]]
-[[Category: Kinase]]
-[[Category: Transferase]]

2acx

From Proteopedia

Current revision

Crystal Structure of G protein coupled receptor kinase 6 bound to AMPPNP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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