3d2u

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{{STRUCTURE_3d2u| PDB=3d2u | SCENE= }}
 
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===Structure of UL18, a Peptide-Binding Viral MHC Mimic, Bound to a Host Inhibitory Receptor===
 
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{{ABSTRACT_PUBMED_18632577}}
 
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==Disease==
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==Structure of UL18, a Peptide-Binding Viral MHC Mimic, Bound to a Host Inhibitory Receptor==
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[[http://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN]] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:[http://omim.org/entry/607371 607371]]. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.<ref>PMID:16685646</ref> Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:[http://omim.org/entry/243310 243310]]. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.<ref>PMID:22366783</ref> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref><ref>PMID:1336137</ref><ref>PMID:7554280</ref><ref>PMID:4586824</ref><ref>PMID:8084451</ref><ref>PMID:12119416</ref><ref>PMID:12796775</ref><ref>PMID:16901902</ref><ref>PMID:16491088</ref><ref>PMID:17646174</ref><ref>PMID:18835253</ref><ref>PMID:18395224</ref><ref>PMID:19284997</ref>
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<StructureSection load='3d2u' size='340' side='right'caption='[[3d2u]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3d2u]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_betaherpesvirus_5 Human betaherpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D2U FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.21&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3d2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d2u OCA], [https://pdbe.org/3d2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d2u RCSB], [https://www.ebi.ac.uk/pdbsum/3d2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d2u ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/UL18_HCMVA UL18_HCMVA] Plays a role in the protection against host NK cell cytotoxicity by interacting with and modulating the activity of the host inhibitory leukocyte Ig-like receptor 1/LILRB1, which is expressed on monocytes, dendritic cells, as well as subsets of T and NK cells. UL18 exerts an inhibitory effect on LIR-1+ NK cells, while it stimulates LIR-1- NK cell. These modulations prevent lysis of the infected cells by NK cells.<ref>PMID:18688275</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d2/3d2u_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3d2u ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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UL18 is a human cytomegalovirus class I MHC (MHCI) homolog that binds the host inhibitory receptor LIR-1 and the only known viral MHC homolog that presents peptides. The 2.2-A structure of a LIR-1/UL18/peptide complex reveals increased contacts and optimal surface complementarity in the LIR-1/UL18 interface compared with LIR/MHCI interfaces, resulting in a &gt;1,000-fold higher affinity. Despite sharing only approximately 25% sequence identity, UL18's structure and peptide binding are surprisingly similar to host MHCI. The crystal structure suggests that most of the UL18 surface, except where LIR-1 and the host-derived light chain bind, is covered by carbohydrates attached to 13 potential N-glycosylation sites, thereby preventing access to bound peptide and association with most MHCI-binding proteins. The LIR-1/UL18 structure demonstrates how a viral protein evolves from its host ancestor to impede unwanted interactions while preserving and improving its receptor-binding site.
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==Function==
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Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor.,Yang Z, Bjorkman PJ Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10095-100. Epub 2008 Jul 15. PMID:18632577<ref>PMID:18632577</ref>
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[[http://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN]] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [[http://www.uniprot.org/uniprot/LIRB1_HUMAN LIRB1_HUMAN]] Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Receptor for H301/UL18, a human cytomegalovirus class I MHC homolog. Ligand binding results in inhibitory signals and down-regulation of the immune response. Engagement of LILRB1 present on natural killer cells or T-cells by class I MHC molecules protects the target cells from lysis. Interaction with HLA-B or HLA-E leads to inhibition of the signal triggered by FCER1A and inhibits serotonin release. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions.<ref>PMID:9285411</ref><ref>PMID:9842885</ref><ref>PMID:11907092</ref> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3d2u]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_herpesvirus_5 Human herpesvirus 5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D2U OCA].
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</div>
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<div class="pdbe-citations 3d2u" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Beta-2 microglobulin|Beta-2 microglobulin]]
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*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
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*[[Leukocyte immunoglobulin-like receptor|Leukocyte immunoglobulin-like receptor]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:018632577</ref><references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Human herpesvirus 5]]
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[[Category: Human betaherpesvirus 5]]
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[[Category: Bjorkman, P J.]]
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[[Category: Large Structures]]
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[[Category: Yang, Z.]]
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[[Category: Bjorkman PJ]]
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[[Category: Disease mutation]]
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[[Category: Yang Z]]
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[[Category: Glycation]]
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[[Category: Glycoprotein]]
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[[Category: Immune response]]
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[[Category: Immune system]]
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[[Category: Immunoglobulin domain]]
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[[Category: Membrane]]
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[[Category: Mhc class i homolog]]
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[[Category: Mhc i]]
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[[Category: Phosphoprotein]]
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[[Category: Pyrrolidone carboxylic acid]]
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[[Category: Receptor]]
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[[Category: Secreted]]
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[[Category: Transmembrane]]
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Current revision

Structure of UL18, a Peptide-Binding Viral MHC Mimic, Bound to a Host Inhibitory Receptor

PDB ID 3d2u

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