View source for 6nyp


==Crystal structure of UL144/BTLA complex==
<StructureSection load='6nyp' size='340' side='right'caption='[[6nyp]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nyp]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Macacine_alphaherpesvirus_1 Macacine alphaherpesvirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NYP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NYP 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6nyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nyp OCA], [https://pdbe.org/6nyp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nyp RCSB], [https://www.ebi.ac.uk/pdbsum/6nyp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nyp ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human cytomegalovirus (HCMV) is a beta-herpesvirus that has co-evolved with the host immune system to establish lifelong persistence. HCMV encodes many immune-modulatory molecules, including the glycoprotein UL144. UL144 is a structural mimic of the TNFRSF member HVEM, which binds to various ligands LIGHT, LTalpha, BTLA, CD160 and gD. However, in contrast to HVEM, UL144 only binds BTLA, inhibiting T cell activation. Here we report the crystal structure of the UL144/BTLA complex, revealing that UL144 utilizes residues from its N-terminal cysteine rich domain 1 (CRD1) to interact uniquely with BTLA. The shorter CRD2 loop of UL144 also alters the relative orientation of BTLA binding with both N-terminal CRDs. Employing structure-guided mutagenesis we have identified a mutant of BTLA (L123A) that interferes with HVEM binding, but preserves UL144 interactions. Furthermore, our results illuminate structural differences between UL144 and HVEM that explain its binding selectivity and highlight it as a suitable scaffold for designing superior, immune inhibitory BTLA agonists.

Structure of human cytomegalovirus UL144, an HVEM orthologue, bound to the B and T cell Lymphocyte Attenuator.,Bitra A, Nemcovicova I, Picarda G, Doukov T, Wang J, Benedict CA, Zajonc DM J Biol Chem. 2019 May 24. pii: RA119.009199. doi: 10.1074/jbc.RA119.009199. PMID:31126984<ref>PMID:31126984</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6nyp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Macacine alphaherpesvirus 1]]
[[Category: Aruna B]]
[[Category: Doukov T]]
[[Category: Zajonc DM]]