View source for 7sk4


==Cryo-EM structure of ACKR3 in complex with chemokine N-terminal mutant CXCL12_LRHQ, an intracellular Fab, and an extracellular Fab==
<StructureSection load='7sk4' size='340' side='right'caption='[[7sk4]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sk4]] is a 6 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=7SK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SK4 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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=7sk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sk4 OCA], [https://pdbe.org/7sk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sk4 RCSB], [https://www.ebi.ac.uk/pdbsum/7sk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sk4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACKR3_HUMAN ACKR3_HUMAN] Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Acts as coreceptor with CXCR4 for a restricted number of HIV isolates.<ref>PMID:16107333</ref> <ref>PMID:16940167</ref> <ref>PMID:17804806</ref> <ref>PMID:18653785</ref> <ref>PMID:19255243</ref> <ref>PMID:19380869</ref> <ref>PMID:19641136</ref> <ref>PMID:20018651</ref> <ref>PMID:20161793</ref> <ref>PMID:20388803</ref> <ref>PMID:20887389</ref> <ref>PMID:22300987</ref> 
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== Publication Abstract from PubMed ==
Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward beta-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs.

,  PMID:35857509<ref>PMID:35857509</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7sk4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gustavsson M]]
[[Category: Handel TM]]
[[Category: Schafer CT]]
[[Category: Tesmer JJG]]
[[Category: Yen YC]]