View source for 8hxc


==Cryo-EM structure of MPXV M2 heptamer in complex with human B7.2==
<StructureSection load='8hxc' size='340' side='right'caption='[[8hxc]], [[Resolution|resolution]] 3.12&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hxc]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Monkeypox_virus Monkeypox virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HXC 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]] 3.12&#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=8hxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hxc OCA], [https://pdbe.org/8hxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hxc RCSB], [https://www.ebi.ac.uk/pdbsum/8hxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hxc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CD86_HUMAN CD86_HUMAN] Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cell activation and costimulation of naive T-cells, such as deciding between immunity and anergy that is made by T-cells within 24 hours after activation. Isoform 2 interferes with the formation of CD86 clusters, and thus acts as a negative regulator of T-cell activation.
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== Publication Abstract from PubMed ==
The rapid spread of monkeypox in multiple countries has resulted in a global public health threat and has caused international concerns since May 2022. Poxvirus encoded M2 protein is a member of the poxvirus immune evasion family and plays roles in host immunomodulation via the regulation of innate immune response mediated by the NF-kappaB pathway and adaptive immune response mediated by B7 ligands. However, the interaction of monkeypox virus (MPXV) M2 with B7 ligands and structural insight into poxviral M2 function have remained elusive. Here we reveal that MPXV M2, co-existing as a hexamer and a heptamer, recognizes human B7.1 and B7.2 (hB7.1/2) with high avidities. The binding of oligomeric MPXV M2 interrupts the interactions of hB7.1/2 with CD28 and CTLA4 and subverts T cell activation mediated by B7.1/2 costimulatory signals. Cryo-EM structures of M2 in complex with hB7.1/2 show that M2 binds to the shallow concave face of hB7.1/2 and displays sterically competition with CD28 and CTLA4 for the binding to hB7.1/2. Our findings provide structural mechanisms of poxviral M2 function and immune evasion deployed by poxviruses.

Structural and functional insights into the modulation of T cell costimulation by monkeypox virus protein M2.,Yang S, Wang Y, Yu F, Cheng R, Zhang Y, Zhou D, Ren X, Deng Z, Zhao H Nat Commun. 2023 Aug 25;14(1):5186. doi: 10.1038/s41467-023-40748-2. PMID:37626059<ref>PMID:37626059</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8hxc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Monkeypox virus]]
[[Category: Deng Z]]
[[Category: Wang Y]]
[[Category: Yang S]]
[[Category: Zhao H]]