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3nyn

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Revision as of 04:20, 25 December 2014

Crystal Structure of G Protein-Coupled Receptor Kinase 6 in Complex with Sangivamycin

Structural highlights

3nyn 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.
Ligands:	, ,
NonStd Res:
Related:	2acx, 3nyo
Gene:	GPRK6, GRK6 (Homo sapiens)
Activity:	[G-protein-coupled_receptor_kinase [G-protein-coupled receptor] kinase], with EC number 2.7.11.16
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

G protein-coupled receptor (GPCR) kinases (GRKs) selectively recognize and are allosterically regulated by activated GPCRs, but the molecular basis for this interaction is not understood. Herein, we report crystal structures of GRK6 in which regions known to be critical for receptor phosphorylation have coalesced to stabilize the kinase domain in a closed state and to form a likely receptor docking site. The crux of this docking site is an extended N-terminal helix that bridges the large and small lobes of the kinase domain and lies adjacent to a basic surface of the protein proposed to bind anionic phospholipids. Mutation of exposed, hydrophobic residues in the N-terminal helix selectively inhibits receptor, but not peptide phosphorylation, suggesting that these residues interact directly with GPCRs. Our structural and biochemical results thus provide an explanation for how receptor recognition, phospholipid binding, and kinase activation are intimately coupled in GRKs.

Molecular basis for activation of G protein-coupled receptor kinases.,Boguth CA, Singh P, Huang CC, Tesmer JJ EMBO J. 2010 Aug 20. PMID:20729810^[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
↑ Boguth CA, Singh P, Huang CC, Tesmer JJ. Molecular basis for activation of G protein-coupled receptor kinases. EMBO J. 2010 Aug 20. PMID:20729810 doi:10.1038/emboj.2010.206

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/3nyn"

@@ Line 10: / Line 10: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nyn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nyn RCSB], [http://www.ebi.ac.uk/pdbsum/3nyn PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://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]]

3nyn

From Proteopedia

Revision as of 04:20, 25 December 2014

Crystal Structure of G Protein-Coupled Receptor Kinase 6 in Complex with Sangivamycin

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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