4jm0

From Proteopedia

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Revision as of 11:17, 4 August 2016

Structure of Human Cytomegalovirus Immune Modulator UL141

Structural highlights

4jm0 is a 2 chain structure with sequence from Hcmvm. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4i9x
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UL141_HCMVM] Evasion of NK cell killing. Blocks surface expression of PVR which is a ligand for NK cell-activating receptors. Binds human PVR in the endoplasmic reticulum and prevents its maturation and transport to the cell surface. Targets also the natural killer cell activating ligand PVRL2/Nectin-2 for proteasome-mediated degradation.^[1]

Publication Abstract from PubMed

Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 A resolution allowed analysis of its head-to-tail dimerization interface. A `dimerization-deficient' mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C'C and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar `lock-and-key' interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X6G `lock' motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host-receptor interactions are evolutionary conserved.

The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding.,Nemcovicova I, Zajonc DM Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):851-62. doi:, 10.1107/S1399004713033750. Epub 2014 Feb 22. PMID:24598754^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Prod'homme V, Sugrue DM, Stanton RJ, Nomoto A, Davies J, Rickards CR, Cochrane D, Moore M, Wilkinson GW, Tomasec P. Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112. J Gen Virol. 2010 Aug;91(Pt 8):2034-9. doi: 10.1099/vir.0.021931-0. Epub 2010 Apr, 21. PMID:20410314 doi:http://dx.doi.org/10.1099/vir.0.021931-0
↑ Nemcovicova I, Zajonc DM. The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding. Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):851-62. doi:, 10.1107/S1399004713033750. Epub 2014 Feb 22. PMID:24598754 doi:http://dx.doi.org/10.1107/S1399004713033750

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4jm0"

@@ Line 1: / Line 1: @@
 ==Structure of Human Cytomegalovirus Immune Modulator UL141==
 <StructureSection load='4jm0' size='340' side='right' caption='[[4jm0]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i9x|4i9x]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jm0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jm0 RCSB], [http://www.ebi.ac.uk/pdbsum/4jm0 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jm0 OCA], [http://pdbe.org/4jm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jm0 RCSB], [http://www.ebi.ac.uk/pdbsum/4jm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jm0 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4jm0" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4jm0

From Proteopedia

Revision as of 11:17, 4 August 2016

Structure of Human Cytomegalovirus Immune Modulator UL141

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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