View source for 6z20


==Structure of the EC2 domain of CD9 in complex with nanobody 4C8==
<StructureSection load='6z20' size='340' side='right'caption='[[6z20]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6z20]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z20 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z20 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.68&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6z20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z20 OCA], [https://pdbe.org/6z20 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z20 RCSB], [https://www.ebi.ac.uk/pdbsum/6z20 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z20 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CD9_HUMAN CD9_HUMAN] Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:8478605, PubMed:14575715, PubMed:18541721). Present at the cell surface of oocytes and plays a key role in sperm-egg fusion, possibly by organizing multiprotein complexes and the morphology of the membrane required for the fusion (By similarity). In myoblasts, associates with CD81 and PTGFRN and inhibits myotube fusion during muscle regeneration (By similarity). In macrophages, associates with CD81 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles (PubMed:12796480). Also prevents the fusion between mononuclear cell progenitors into osteoclasts in charge of bone resorption (By similarity). Acts as a receptor for PSG17 (By similarity). Involved in platelet activation and aggregation (PubMed:18541721). Regulates paranodal junction formation (By similarity). Involved in cell adhesion, cell motility and tumor metastasis (PubMed:8478605, PubMed:7511626).[UniProtKB:P40240]<ref>PMID:12796480</ref> <ref>PMID:14575715</ref> <ref>PMID:18541721</ref> <ref>PMID:7511626</ref> <ref>PMID:8478605</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tetraspanins are eukaryotic membrane proteins that contribute to a variety of signaling processes by organizing partner-receptor molecules in the plasma membrane. How tetraspanins bind and cluster partner receptors into tetraspanin-enriched microdomains is unknown. Here, we present crystal structures of the large extracellular loop of CD9 bound to nanobodies 4C8 and 4E8 and, the cryo-EM structure of 4C8-bound CD9 in complex with its partner EWI-F. CD9-EWI-F displays a tetrameric arrangement with two central EWI-F molecules, dimerized through their ectodomains, and two CD9 molecules, one bound to each EWI-F transmembrane helix through CD9-helices h3 and h4. In the crystal structures, nanobodies 4C8 and 4E8 bind CD9 at loops C and D, which is in agreement with the 4C8 conformation in the CD9-EWI-F complex. The complex varies from nearly twofold symmetric (with the two CD9 copies nearly anti-parallel) to ca. 50 degrees bent arrangements. This flexible arrangement of CD9-EWI-F with potential CD9 homo-dimerization at either end provides a "concatenation model" for forming short linear or circular assemblies, which may explain the occurrence of tetraspanin-enriched microdomains.

Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F.,Oosterheert W, Xenaki KT, Neviani V, Pos W, Doulkeridou S, Manshande J, Pearce NM, Kroon-Batenburg LM, Lutz M, van Bergen En Henegouwen PM, Gros P Life Sci Alliance. 2020 Sep 21;3(11). pii: 3/11/e202000883. doi:, 10.26508/lsa.202000883. Print 2020 Nov. PMID:32958604<ref>PMID:32958604</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6z20" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Gros P]]
[[Category: Lutz M]]
[[Category: Manshande J]]
[[Category: Oosterheert W]]
[[Category: Pearce NM]]