8zjg
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of human CMKLR1-Gi complex bound to chemerin== | |
| + | <StructureSection load='8zjg' size='340' side='right'caption='[[8zjg]], [[Resolution|resolution]] 3.18Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8zjg]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZJG 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]] 3.18Å</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=8zjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zjg OCA], [https://pdbe.org/8zjg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zjg RCSB], [https://www.ebi.ac.uk/pdbsum/8zjg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zjg ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CML1_HUMAN CML1_HUMAN] Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with RARRES2 initiates activation of G proteins G(i)/G(o) and beta-arrestin pathways inducing cellular responses via second messenger pathways such as intracellular calcium mobilization, phosphorylation of MAP kinases MAPK1/MAPK3 (ERK1/2), TYRO3, MAPK14/P38MAPK and PI3K leading to multifunctional effects, like reduction of immune responses, enhancing of adipogenesis and angionesis (PubMed:27716822). Resolvin E1 down-regulates cytokine production in macrophages by reducing the activation of MAPK1/3 (ERK1/2) and NF-kappa-B. Positively regulates adipogenesis and adipocyte metabolism.<ref>PMID:15728234</ref> <ref>PMID:15753205</ref> <ref>PMID:20044979</ref> <ref>PMID:27716822</ref> (Microbial infection) Acts as a coreceptor for several SIV strains (SIVMAC316, SIVMAC239, SIVMACL7E-FR and SIVSM62A), as well as a primary HIV-1 strain (92UG024-2).<ref>PMID:9603476</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Chemerin, a chemotactic adipokine, plays essential roles in adipogenesis and inflammation. Serum chemerin concentration is closely associated with obesity and metabolism disorders. The mature form of chemerin (residues 21-157) acts primarily through chemerin receptor 1 (CMKLR1) for transmembrane signaling. As a result, CMKLR1 serves as a promising target for therapeutic intervention of immunometabolic diseases such as diabetes and multiple sclerosis. Here, we present a high-resolution cryo-EM structure of CMKLR1-Gi signaling complex bound to biologically active full-length chemerin. The mature chemerin shows binding features distinct from its C-terminal nonapeptide including interaction with both the extracellular loops (ECLs) and the N-terminus of CMKLR1. Combining results from functional assays, our studies demonstrate that chemerin interacts with CMKLR1 in a "two-site" mode similar to chemokine-chemokine receptor interactions, but acting as a "reverse chemokine" by inserting its C-terminus instead of the N-terminus as in the case of chemokines into the transmembrane binding pocket of CMKLR1. These structural insights are expected to help develop synthetic analogs with therapeutic potential. | ||
| - | + | Structural basis for full-length chemerin recognition and signaling through chemerin receptor 1.,Liu A, Liu Y, Wang J, Ye RD Commun Biol. 2024 Nov 30;7(1):1598. doi: 10.1038/s42003-024-07228-9. PMID:39616240<ref>PMID:39616240</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8zjg" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Liu | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Vicugna pacos]] | ||
| + | [[Category: Liu AJ]] | ||
| + | [[Category: Liu YZ]] | ||
| + | [[Category: Ye RD]] | ||
Current revision
Cryo-EM structure of human CMKLR1-Gi complex bound to chemerin
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Categories: Homo sapiens | Large Structures | Vicugna pacos | Liu AJ | Liu YZ | Ye RD
