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| | <StructureSection load='5tez' size='340' side='right'caption='[[5tez]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='5tez' size='340' side='right'caption='[[5tez]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tez]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TEZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tez]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TEZ FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-A, HLAA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</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=5tez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tez OCA], [http://pdbe.org/5tez PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tez RCSB], [http://www.ebi.ac.uk/pdbsum/5tez PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tez ProSAT]</span></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=5tez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tez OCA], [https://pdbe.org/5tez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tez RCSB], [https://www.ebi.ac.uk/pdbsum/5tez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tez ProSAT]</span></td></tr> |
| | </table> | | </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 == | | == Function == |
| - | [[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. [[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. | + | [https://www.uniprot.org/uniprot/M1_I34A1 M1_I34A1] Plays critical roles in virus replication, from virus entry and uncoating to assembly and budding of the virus particle. M1 binding to ribonucleocapsids (RNPs) in nucleus seems to inhibit viral transcription. Interaction of viral NEP with M1-RNP is thought to promote nuclear export of the complex, which is targeted to the virion assembly site at the apical plasma membrane in polarized epithelial cells. Interactions with NA and HA may bring M1, a non-raft-associated protein, into lipid rafts. Forms a continuous shell on the inner side of the lipid bilayer in virion, where it binds the RNP. During virus entry into cell, the M2 ion channel acidifies the internal virion core, inducing M1 dissociation from the RNP. M1-free RNPs are transported to the nucleus, where viral transcription and replication can take place.<ref>PMID:11531417</ref> Determines the virion's shape: spherical or filamentous. Clinical isolates of influenza are characterized by the presence of significant proportion of filamentous virions, whereas after multiple passage on eggs or cell culture, virions have only spherical morphology. Filamentous virions are thought to be important to infect neighboring cells, and spherical virions more suited to spread through aerosol between hosts organisms.<ref>PMID:11531417</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | + | [[Category: Influenza A virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mariuzza, R A]] | + | [[Category: Mariuzza RA]] |
| - | [[Category: Yang, X]] | + | [[Category: Yang X]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Tcr flu m1-hla-a2]]
| + | |
| Structural highlights
Function
M1_I34A1 Plays critical roles in virus replication, from virus entry and uncoating to assembly and budding of the virus particle. M1 binding to ribonucleocapsids (RNPs) in nucleus seems to inhibit viral transcription. Interaction of viral NEP with M1-RNP is thought to promote nuclear export of the complex, which is targeted to the virion assembly site at the apical plasma membrane in polarized epithelial cells. Interactions with NA and HA may bring M1, a non-raft-associated protein, into lipid rafts. Forms a continuous shell on the inner side of the lipid bilayer in virion, where it binds the RNP. During virus entry into cell, the M2 ion channel acidifies the internal virion core, inducing M1 dissociation from the RNP. M1-free RNPs are transported to the nucleus, where viral transcription and replication can take place.[1] Determines the virion's shape: spherical or filamentous. Clinical isolates of influenza are characterized by the presence of significant proportion of filamentous virions, whereas after multiple passage on eggs or cell culture, virions have only spherical morphology. Filamentous virions are thought to be important to infect neighboring cells, and spherical virions more suited to spread through aerosol between hosts organisms.[2]
Publication Abstract from PubMed
Influenza A virus (IAV) causes an acute infection in humans that is normally eliminated by CD8+ cytotoxic T lymphocytes. Individuals expressing the major histocompatibility complex (MHC) class I molecule HLA-A2 produce cytotoxic T lymphocytes bearing T cell receptors (TCRs) that recognize the immunodominant IAV epitope GILGFVFTL (GIL). Most GIL-specific TCRs utilize alpha/beta pairs encoded by the TRAV27/TRBV19 gene combination to recognize this relatively featureless peptide epitope (canonical TCRs). However, ~40% of GIL-specific TCRs express a wide variety of other TRAV/TRBV combinations (non-canonical TCRs). To investigate the structural underpinnings of this remarkable diversity, we determined the crystal structure of a non-canonical GIL-specific TCR (F50) expressing the TRAV13-1/TRBV27 gene combination bound to GIL-HLA-A2 to 1.7 A resolution. Comparison of the F50-GIL-HLA-A2 complex with the previously publishedcomplex formed by a canonical TCR (JM22) revealed that F50 and JM22 engage GIL-HLA-A2 in markedly different orientations. These orientations are distinguished by crossing angles of TCR to peptide-MHC of 29o for F50 versus 69o for JM22, and by a focus by F50 on the C-terminus rather than the center of the MHC alpha1 helix for JM22. In addition, F50, unlike JM22, uses a tryptophan instead of an arginine to fill a critical notch between GIL and the HLA-A2 alpha 2 helix. The F50-GIL-HLA-A2 complex shows that there are multiple structurally distinct solutions to recognizing an identical peptide-MHC ligand with sufficient affinity to elicit a broad anti-IAV response that protects against viral escape and T cell clonal loss.
Structural basis for clonal diversity of the human T cell response to a dominant influenza virus epitope.,Yang X, Chen G, Weng NP, Mariuzza RA J Biol Chem. 2017 Sep 20. pii: jbc.M117.810382. doi: 10.1074/jbc.M117.810382. PMID:28931605[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang X, Liu T, Muller J, Levandowski RA, Ye Z. Effect of influenza virus matrix protein and viral RNA on ribonucleoprotein formation and nuclear export. Virology. 2001 Sep 1;287(2):405-16. PMID:11531417 doi:10.1006/viro.2001.1067
- ↑ Huang X, Liu T, Muller J, Levandowski RA, Ye Z. Effect of influenza virus matrix protein and viral RNA on ribonucleoprotein formation and nuclear export. Virology. 2001 Sep 1;287(2):405-16. PMID:11531417 doi:10.1006/viro.2001.1067
- ↑ Yang X, Chen G, Weng NP, Mariuzza RA. Structural basis for clonal diversity of the human T cell response to a dominant influenza virus epitope. J Biol Chem. 2017 Sep 20. pii: jbc.M117.810382. doi: 10.1074/jbc.M117.810382. PMID:28931605 doi:http://dx.doi.org/10.1074/jbc.M117.810382
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