8ic0: Difference between revisions
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==Cryo-EM structure of CXCL8 bound C-X-C chemokine receptor 1 in complex with Gi heterotrimer== | |||
<StructureSection load='8ic0' size='340' side='right'caption='[[8ic0]], [[Resolution|resolution]] 3.41Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ic0]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IC0 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]] 3.41Å</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=8ic0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ic0 OCA], [https://pdbe.org/8ic0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ic0 RCSB], [https://www.ebi.ac.uk/pdbsum/8ic0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ic0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CXCR1_HUMAN CXCR1_HUMAN] Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Neutrophil granulocytes play key roles in innate immunity and shaping adaptive immune responses. They are attracted by chemokines to sites of infection and tissue damage, where they kill and phagocytose bacteria. The chemokine CXCL8 (also known as interleukin-8, abbreviated IL-8) and its G-protein-coupled receptors CXCR1 and CXCR2 are crucial elements in this process, and also the development of many cancers. These GPCRs have therefore been the target of many drug development campaigns and structural studies. Here, we solve the structure of CXCR1 complexed with CXCL8 and cognate G-proteins using cryo-EM, showing the detailed interactions between the receptor, the chemokine and Galphai protein. Unlike the closely related CXCR2, CXCR1 strongly prefers to bind CXCL8 in its monomeric form. The model shows that steric clashes would form between dimeric CXCL8 and extracellular loop 2 (ECL2) of CXCR1. Consistently, transplanting ECL2 of CXCR2 onto CXCR1 abolishes the selectivity for the monomeric chemokine. Our model and functional analysis of various CXCR1 mutants will assist efforts in structure-based drug design targeting specific CXC chemokine receptor subtypes. | |||
Structural basis of CXC chemokine receptor 1 ligand binding and activation.,Ishimoto N, Park JH, Kawakami K, Tajiri M, Mizutani K, Akashi S, Tame JRH, Inoue A, Park SY Nat Commun. 2023 Jul 11;14(1):4107. doi: 10.1038/s41467-023-39799-2. PMID:37433790<ref>PMID:37433790</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8ic0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Ishimoto N]] | |||
[[Category: Park JH]] | |||
[[Category: Park SY]] | |||
Latest revision as of 09:15, 19 July 2023
Cryo-EM structure of CXCL8 bound C-X-C chemokine receptor 1 in complex with Gi heterotrimerCryo-EM structure of CXCL8 bound C-X-C chemokine receptor 1 in complex with Gi heterotrimer
Structural highlights
FunctionCXCR1_HUMAN Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity. Publication Abstract from PubMedNeutrophil granulocytes play key roles in innate immunity and shaping adaptive immune responses. They are attracted by chemokines to sites of infection and tissue damage, where they kill and phagocytose bacteria. The chemokine CXCL8 (also known as interleukin-8, abbreviated IL-8) and its G-protein-coupled receptors CXCR1 and CXCR2 are crucial elements in this process, and also the development of many cancers. These GPCRs have therefore been the target of many drug development campaigns and structural studies. Here, we solve the structure of CXCR1 complexed with CXCL8 and cognate G-proteins using cryo-EM, showing the detailed interactions between the receptor, the chemokine and Galphai protein. Unlike the closely related CXCR2, CXCR1 strongly prefers to bind CXCL8 in its monomeric form. The model shows that steric clashes would form between dimeric CXCL8 and extracellular loop 2 (ECL2) of CXCR1. Consistently, transplanting ECL2 of CXCR2 onto CXCR1 abolishes the selectivity for the monomeric chemokine. Our model and functional analysis of various CXCR1 mutants will assist efforts in structure-based drug design targeting specific CXC chemokine receptor subtypes. Structural basis of CXC chemokine receptor 1 ligand binding and activation.,Ishimoto N, Park JH, Kawakami K, Tajiri M, Mizutani K, Akashi S, Tame JRH, Inoue A, Park SY Nat Commun. 2023 Jul 11;14(1):4107. doi: 10.1038/s41467-023-39799-2. PMID:37433790[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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