7mta: Difference between revisions
New page: '''Unreleased structure''' The entry 7mta is ON HOLD Authors: Chen, Q., Chen, C.-L., Tesmer, J.J.G. Description: Rhodopsin kinase (GRK1)-S5E/S488E/T489E in complex with rhodopsin and F... |
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The | ==Rhodopsin kinase (GRK1)-S5E/S488E/T489E in complex with rhodopsin and Fab1== | ||
<StructureSection load='7mta' size='340' side='right'caption='[[7mta]], [[Resolution|resolution]] 4.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7mta]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MTA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1Å, 6 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RET:RETINAL'>RET</scene>, <scene name='pdbligand=SGV:SANGIVAMYCIN'>SGV</scene></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=7mta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mta OCA], [https://pdbe.org/7mta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mta RCSB], [https://www.ebi.ac.uk/pdbsum/7mta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mta ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GRK1_BOVIN GRK1_BOVIN] Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade (PubMed:12686556, PubMed:16675451, PubMed:21299498). This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination (By similarity). May play a role in the maintenance of the outer nuclear layer in the retina (By similarity).[UniProtKB:Q9WVL4]<ref>PMID:12686556</ref> <ref>PMID:16675451</ref> <ref>PMID:21299498</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
G-protein-coupled receptor (GPCR) kinases (GRKs) selectively phosphorylate activated GPCRs, thereby priming them for desensitization(1). Although it is unclear how GRKs recognize these receptors(2-4), a conserved region at the GRK N terminus is essential for this process(5-8). Here we report a series of cryo-electron microscopy single-particle reconstructions of light-activated rhodopsin (Rho*) bound to rhodopsin kinase (GRK1), wherein the N terminus of GRK1 forms a helix that docks into the open cytoplasmic cleft of Rho*. The helix also packs against the GRK1 kinase domain and stabilizes it in an active configuration. The complex is further stabilized by electrostatic interactions between basic residues that are conserved in most GPCRs and acidic residues that are conserved in GRKs. We did not observe any density for the regulator of G-protein signalling homology domain of GRK1 or the C terminus of rhodopsin. Crosslinking with mass spectrometry analysis confirmed these results and revealed dynamic behaviour in receptor-bound GRK1 that would allow the phosphorylation of multiple sites in the receptor tail. We have identified GRK1 residues whose mutation augments kinase activity and crosslinking with Rho*, as well as residues that are involved in activation by acidic phospholipids. From these data, we present a general model for how a small family of protein kinases can recognize and be activated by hundreds of different GPCRs. | |||
Structures of rhodopsin in complex with G-protein-coupled receptor kinase 1.,Chen Q, Plasencia M, Li Z, Mukherjee S, Patra D, Chen CL, Klose T, Yao XQ, Kossiakoff AA, Chang L, Andrews PC, Tesmer JJG Nature. 2021 Jul;595(7868):600-605. doi: 10.1038/s41586-021-03721-x. Epub 2021 , Jul 14. PMID:34262173<ref>PMID:34262173</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7mta" style="background-color:#fffaf0;"></div> | ||
[[Category: Chen | |||
[[Category: Chen | ==See Also== | ||
*[[Rhodopsin kinase|Rhodopsin kinase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen C-L]] | |||
[[Category: Chen Q]] | |||
[[Category: Tesmer JJG]] | |||
Latest revision as of 16:44, 6 November 2024
Rhodopsin kinase (GRK1)-S5E/S488E/T489E in complex with rhodopsin and Fab1Rhodopsin kinase (GRK1)-S5E/S488E/T489E in complex with rhodopsin and Fab1
Structural highlights
FunctionGRK1_BOVIN Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade (PubMed:12686556, PubMed:16675451, PubMed:21299498). This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination (By similarity). May play a role in the maintenance of the outer nuclear layer in the retina (By similarity).[UniProtKB:Q9WVL4][1] [2] [3] Publication Abstract from PubMedG-protein-coupled receptor (GPCR) kinases (GRKs) selectively phosphorylate activated GPCRs, thereby priming them for desensitization(1). Although it is unclear how GRKs recognize these receptors(2-4), a conserved region at the GRK N terminus is essential for this process(5-8). Here we report a series of cryo-electron microscopy single-particle reconstructions of light-activated rhodopsin (Rho*) bound to rhodopsin kinase (GRK1), wherein the N terminus of GRK1 forms a helix that docks into the open cytoplasmic cleft of Rho*. The helix also packs against the GRK1 kinase domain and stabilizes it in an active configuration. The complex is further stabilized by electrostatic interactions between basic residues that are conserved in most GPCRs and acidic residues that are conserved in GRKs. We did not observe any density for the regulator of G-protein signalling homology domain of GRK1 or the C terminus of rhodopsin. Crosslinking with mass spectrometry analysis confirmed these results and revealed dynamic behaviour in receptor-bound GRK1 that would allow the phosphorylation of multiple sites in the receptor tail. We have identified GRK1 residues whose mutation augments kinase activity and crosslinking with Rho*, as well as residues that are involved in activation by acidic phospholipids. From these data, we present a general model for how a small family of protein kinases can recognize and be activated by hundreds of different GPCRs. Structures of rhodopsin in complex with G-protein-coupled receptor kinase 1.,Chen Q, Plasencia M, Li Z, Mukherjee S, Patra D, Chen CL, Klose T, Yao XQ, Kossiakoff AA, Chang L, Andrews PC, Tesmer JJG Nature. 2021 Jul;595(7868):600-605. doi: 10.1038/s41586-021-03721-x. Epub 2021 , Jul 14. PMID:34262173[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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