8yu7
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of CXCR4 tetramer== | |
| + | <StructureSection load='8yu7' size='340' side='right'caption='[[8yu7]], [[Resolution|resolution]] 3.01Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8yu7]] is a 4 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=8YU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8YU7 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]] 3.01Å</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=8yu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8yu7 OCA], [https://pdbe.org/8yu7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8yu7 RCSB], [https://www.ebi.ac.uk/pdbsum/8yu7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8yu7 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CXCR4_HUMAN CXCR4_HUMAN] Defects in CXCR4 are a cause of WHIM syndrome (WHIM) [MIM:[https://omim.org/entry/193670 193670]; also known as warts, hypogammaglobulinemia, infections and myelokathexis. WHIM syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis.<ref>PMID:12692554</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CXCR4_HUMAN CXCR4_HUMAN] Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus.<ref>PMID:8329116</ref> <ref>PMID:8234909</ref> <ref>PMID:8629022</ref> <ref>PMID:8752280</ref> <ref>PMID:8752281</ref> <ref>PMID:10074102</ref> <ref>PMID:10644702</ref> <ref>PMID:10825158</ref> <ref>PMID:17197449</ref> <ref>PMID:20048153</ref> <ref>PMID:20228059</ref> <ref>PMID:20505072</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | CXC chemokine receptor 4 (CXCR4) is a well-established drug target and a key representative of the chemokine receptor family. Chemokine receptors tend to assemble, and this assembly plays a critical role in regulating their functions. However, structural information regarding the organization of these receptors remains limited. Here, we present the cryoelectron microscopy (cryo-EM) structure of a CXCR4 homo-tetramer. In this tetramer, each protomer interfaces with adjacent protomers via TM1/2 and TM5/6/7, aligning at a 90 degrees angle to assemble into a C4 rotationally symmetric arrangement. Each protomer allosterically regulates the others, with Q272 in the ECL3 loop interacting with K38 (TM1) and V99 (TM2) of the adjacent protomer, resulting in a mutually inhibitory configuration. These findings reveal an allosteric and antagonistic mechanism that prevents excessive activation, providing a structural framework for understanding the molecular mechanisms driving CXCR4 self-assembly and offering insights that could inspire further therapeutic strategies. | ||
| - | + | Structural basis of CXCR4 assembly and regulation.,Liu A, Liu Y, Ye RD Cell Rep. 2025 Feb 25;44(2):115255. doi: 10.1016/j.celrep.2025.115255. Epub 2025 , Jan 31. PMID:39891908<ref>PMID:39891908</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Liu | + | <div class="pdbe-citations 8yu7" style="background-color:#fffaf0;"></div> |
| - | [[Category: Liu | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Liu A]] | ||
| + | [[Category: Liu Y]] | ||
Current revision
Cryo-EM structure of CXCR4 tetramer
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