4hkj
From Proteopedia
(Difference between revisions)
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| - | + | ==Structure of Cowpox CPXV203 in complex with MHCI (H-2Kb)== | |
| - | + | <StructureSection load='4hkj' size='340' side='right' caption='[[4hkj]], [[Resolution|resolution]] 3.00Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[4hkj]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Cowpox_virus_(brighton_red) Cowpox virus (brighton red)], [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HKJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">H-2KB, H2-K, H2-K1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), B2M, BETA-2 MICROGLOBULIN, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CPXV203, CPXV203 CDS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=265872 Cowpox virus (Brighton Red)])</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=4hkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hkj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hkj RCSB], [http://www.ebi.ac.uk/pdbsum/4hkj PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[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> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/HA1B_MOUSE HA1B_MOUSE]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/OVAL_CHICK OVAL_CHICK]] Non-inhibitory serpin. Storage protein of egg white.<ref>PMID:6749856</ref> <ref>PMID:3732511</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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | One of the hallmarks of viral immune evasion is the capacity to disrupt major histocompatibility complex class I (MHCI) antigen presentation to evade T-cell detection. Cowpox virus encoded protein CPXV203 blocks MHCI surface expression by exploiting the KDEL-receptor recycling pathway, and here we show that CPXV203 directly binds a wide array of fully assembled MHCI proteins, both classical and non-classical. Further, the stability of CPXV203/MHCI complexes is highly pH dependent, with dramatically increased affinities at the lower pH of the Golgi relative to the endoplasmic reticulum (ER). Crystallographic studies reveal that CPXV203 adopts a beta-sandwich fold similar to poxvirus chemokine binding proteins, and binds the same highly conserved MHCI determinants located under the peptide-binding platform that tapasin, CD8, and natural killer (NK)-receptors engage. Mutagenesis of the CPXV203/MHCI interface identified the importance of two CPXV203 His residues that confer low pH stabilization of the complex and are critical to ER retrieval of MHCI. These studies clarify mechanistically how CPXV203 coordinates with other cowpox proteins to thwart antigen presentation. | ||
| - | + | Structural Mechanism of ER Retrieval of MHC Class I by Cowpox.,McCoy WH 4th, Wang X, Yokoyama WM, Hansen TH, Fremont DH PLoS Biol. 2012 Nov;10(11):e1001432. doi: 10.1371/journal.pbio.1001432. Epub 2012, Nov 27. PMID:23209377<ref>PMID:23209377</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Beta-2 microglobulin|Beta-2 microglobulin]] | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | <references | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
| - | [[Category: | + | [[Category: Structural genomic]] |
| - | [[Category: Fremont, D H | + | [[Category: Fremont, D H]] |
| - | [[Category: IV, W H.McCoy | + | [[Category: IV, W H.McCoy]] |
[[Category: Antigen presentation]] | [[Category: Antigen presentation]] | ||
| - | [[Category: Center for structural genomics of infectious disease]] | ||
[[Category: Csgid]] | [[Category: Csgid]] | ||
[[Category: Immune system-viral protein complex]] | [[Category: Immune system-viral protein complex]] | ||
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[[Category: National institute of allergy and infectious disease]] | [[Category: National institute of allergy and infectious disease]] | ||
[[Category: Niaid]] | [[Category: Niaid]] | ||
| - | [[Category: Structural genomic]] | ||
[[Category: Viral immune evasion protein]] | [[Category: Viral immune evasion protein]] | ||
Revision as of 07:23, 15 February 2015
Structure of Cowpox CPXV203 in complex with MHCI (H-2Kb)
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