View source for 8tlm


==Structure of a class A GPCR/Fab complex==
<StructureSection load='8tlm' size='340' side='right'caption='[[8tlm]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8tlm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TLM 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]] 2.9&#8491;</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=8tlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tlm OCA], [https://pdbe.org/8tlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tlm RCSB], [https://www.ebi.ac.uk/pdbsum/8tlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tlm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.[https://www.uniprot.org/uniprot/CCR8_HUMAN CCR8_HUMAN] Receptor for the chemokine CCL1/SCYA1/I-309. May regulate monocyte chemotaxis and thymic cell line apoptosis. Alternative coreceptor with CD4 for HIV-1 infection.<ref>PMID:10540332</ref> <ref>PMID:9207005</ref> <ref>PMID:9469461</ref> <ref>PMID:9521068</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein coupled receptor that has emerged as a promising therapeutic target in cancer. Targeting CCR8 with an antibody has appeared to be an attractive therapeutic approach, but the molecular basis for chemokine-mediated activation and antibody-mediated inhibition of CCR8 are not fully elucidated. Here, we obtain an antagonist antibody against human CCR8 and determine structures of CCR8 in complex with either the antibody or the endogenous agonist ligand CCL1. Our studies reveal characteristic antibody features allowing recognition of the CCR8 extracellular loops and CCL1-CCR8 interaction modes that are distinct from other chemokine receptor - ligand pairs. Informed by these structural insights, we demonstrate that CCL1 follows a two-step, two-site binding sequence to CCR8 and that antibody-mediated inhibition of CCL1 signaling can occur by preventing the second binding event. Together, our results provide a detailed structural and mechanistic framework of CCR8 activation and inhibition that expands our molecular understanding of chemokine - receptor interactions and offers insight into the development of therapeutic antibodies targeting chemokine GPCRs.

Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8.,Sun D, Sun Y, Janezic E, Zhou T, Johnson M, Azumaya C, Noreng S, Chiu C, Seki A, Arenzana TL, Nicoludis JM, Shi Y, Wang B, Ho H, Joshi P, Tam C, Payandeh J, Comps-Agrar L, Wang J, Rutz S, Koerber JT, Masureel M Nat Commun. 2023 Dec 1;14(1):7940. doi: 10.1038/s41467-023-43601-8. PMID:38040762<ref>PMID:38040762</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8tlm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aequorea victoria]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Johnson M]]
[[Category: Masureel M]]
[[Category: Sun D]]