4nqv

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{{STRUCTURE_4nqv| PDB=4nqv | SCENE= }}
 
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===Crystal Structure of HLA A*0101 in complex with NP44, an 9-mer influenza epitope===
 
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==Disease==
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==Crystal Structure of HLA A*0101 in complex with NP44, an 9-mer influenza epitope==
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[[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='4nqv' size='340' side='right'caption='[[4nqv]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4nqv]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/H7N9_subtype H7N9 subtype] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NQV 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]] 2.39&#8491;</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=4nqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nqv OCA], [https://pdbe.org/4nqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nqv RCSB], [https://www.ebi.ac.uk/pdbsum/4nqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nqv ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NCAP_I34A1 NCAP_I34A1] Encapsidates the negative strand viral RNA, protecting it from nucleases. The encapsidated genomic RNA is termed the ribonucleoprotein (RNP) and serves as template for transcription and replication. The RNP needs to be localized in the nucleus to start an infectious cycle, but is too large to diffuse through the nuclear pore complex. NP comprises at least 2 nuclear localization signals and is responsible of the active RNP import into the nucleus through the cellular importin alpha/beta pathway. Later in the infection, nucleus export of RNP are mediated through viral proteins NEP interacting with M1 which binds nucleoproteins. It is possible that the nucleoprotein binds directly exportin-1 (XPO1) and plays an active role in RNP nuclear export. M1 interaction with RNP seems to hide nucleoprotein's nuclear localization signals. Soon after a virion infects a new cell, M1 dissociates from the RNP under acidification of the virion driven by M2 protein. Dissociation of M1 from RNP unmask nucleoprotein's nuclear localization signals, targeting the RNP to the nucleus.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The absence of preexisting neutralizing antibodies specific for the novel A (H7N9) influenza virus indicates a lack of prior human exposure. As influenza A virus-specific CD8(+) T lymphocytes (CTLs) can be broadly cross-reactive, we tested whether immunogenic peptides derived from H7N9 might be recognized by memory CTLs established following infection with other influenza strains. Probing across multiple ethnicities, we identified 32 conserved epitopes derived from the nucleoprotein (NP) and matrix-1 (M1) proteins. These NP and M1 peptides are presented by HLAs prevalent in 16-57% of individuals. Remarkably, some HLA alleles (A*0201, A*0301, B*5701, B*1801, and B*0801) elicit robust CTL responses against any human influenza A virus, including H7N9, whereas ethnicities where HLA-A*0101, A*6801, B*1501, and A*2402 are prominent, show limited CTL response profiles. By this criterion, some groups, especially the Alaskan and Australian Indigenous peoples, would be particularly vulnerable to H7N9 infection. This dissection of CTL-mediated immunity to H7N9 thus suggests strategies for both vaccine delivery and development.
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==Function==
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Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities.,Quinones-Parra S, Grant E, Loh L, Nguyen TH, Campbell KA, Tong SY, Miller A, Doherty PC, Vijaykrishna D, Rossjohn J, Gras S, Kedzierska K Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1049-54. doi:, 10.1073/pnas.1322229111. Epub 2014 Jan 6. PMID:24395804<ref>PMID:24395804</ref>
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[[http://www.uniprot.org/uniprot/1A01_HUMAN 1A01_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[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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[[4nqv]] is a 18 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NQV OCA].
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</div>
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<div class="pdbe-citations 4nqv" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<references group="xtra"/><references/>
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*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
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[[Category: Gras, S.]]
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== References ==
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[[Category: Rossjohn, J.]]
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<references/>
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[[Category: Hla presenting h7n9 viral epitope]]
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__TOC__
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[[Category: Immune system]]
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</StructureSection>
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[[Category: Immune system-viral protein complex]]
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[[Category: H7N9 subtype]]
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[[Category: T cell receptor]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Gras S]]
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[[Category: Rossjohn J]]

Current revision

Crystal Structure of HLA A*0101 in complex with NP44, an 9-mer influenza epitope

PDB ID 4nqv

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