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| | <StructureSection load='6nca' size='340' side='right'caption='[[6nca]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='6nca' size='340' side='right'caption='[[6nca]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nca]] is a 60 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=6NCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NCA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nca]] is a 60 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_4 Human gammaherpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NCA 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]] 3.300001Å</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=6nca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nca OCA], [http://pdbe.org/6nca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nca RCSB], [http://www.ebi.ac.uk/pdbsum/6nca PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nca 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=6nca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nca OCA], [https://pdbe.org/6nca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nca RCSB], [https://www.ebi.ac.uk/pdbsum/6nca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nca 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/RTA_EBVG RTA_EBVG]] Immediate-early transcription factor that controls the initiation of viral lytic gene expression and lytic reactivation from latency. Triggers lytic replication, and initiates a cellular senescence program in epithelial cells. Upregulates human DCR3/TNFRSF6B by directly binding to its receptor (By similarity). [[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/BRLF1_EBVG BRLF1_EBVG] Immediate-early transcription factor that controls the initiation of viral lytic gene expression and lytic reactivation from latency. Triggers lytic replication, and initiates a cellular senescence program in epithelial cells. Up-regulates human DCR3/TNFRSF6B by directly binding to its receptor. Globally induces a proteasome-dependent loss of SUMOylated proteins in the host cell and the loss of promeylocytic leukemia nuclear bodies. Improves the stability of the triplex capsid protein TRX1 by reducing the ubiquitination level of the latter. Mediates evasion of inflammasome activation and antiviral responses (T- and NK cell activation) during EBV early lytic infection.[UniProtKB:P03209] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6nca" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6nca" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | + | *[[MHC 3D structures|MHC 3D structures]] |
| | + | *[[MHC I 3D structures|MHC I 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | + | [[Category: Human gammaherpesvirus 4]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Selin, L K]] | + | [[Category: Selin LK]] |
| - | [[Category: Song, I Y]] | + | [[Category: Song IY]] |
| - | [[Category: Stern, L J]] | + | [[Category: Stern LJ]] |
| - | [[Category: Brlf1]]
| + | |
| - | [[Category: Ebv viral peptide]]
| + | |
| - | [[Category: Hla-a2]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
BRLF1_EBVG Immediate-early transcription factor that controls the initiation of viral lytic gene expression and lytic reactivation from latency. Triggers lytic replication, and initiates a cellular senescence program in epithelial cells. Up-regulates human DCR3/TNFRSF6B by directly binding to its receptor. Globally induces a proteasome-dependent loss of SUMOylated proteins in the host cell and the loss of promeylocytic leukemia nuclear bodies. Improves the stability of the triplex capsid protein TRX1 by reducing the ubiquitination level of the latter. Mediates evasion of inflammasome activation and antiviral responses (T- and NK cell activation) during EBV early lytic infection.[UniProtKB:P03209]
Publication Abstract from PubMed
The T cell receptor (TCR) repertoire is an essential component of the CD8 T-cell immune response. Here, we seek to investigate factors that drive selection of TCR repertoires specific to the HLA-A2-restricted immunodominant epitope BRLF1109-117 (YVLDHLIVV) over the course of primary Epstein Barr virus (EBV) infection. Using single-cell paired TCRalphabeta sequencing of tetramer sorted CD8 T cells ex vivo, we show at the clonal level that recognition of the HLA-A2-restricted BRLF1 (YVL-BR, BRLF-1109) epitope is mainly driven by the TCRalpha chain. For the first time, we identify a CDR3alpha (complementarity determining region 3 alpha) motif, KDTDKL, resulting from an obligate AV8.1-AJ34 pairing that was shared by all four individuals studied. This observation coupled with the fact that this public AV8.1-KDTDKL-AJ34 TCR pairs with multiple different TCRbeta chains within the same donor (median 4; range: 1-9), suggests that there are some unique structural features of the interaction between the YVL-BR/MHC and the AV8.1-KDTDKL-AJ34 TCR that leads to this high level of selection. Newly developed TCR motif algorithms identified a lysine at position 1 of the CDR3alpha motif that is highly conserved and likely important for antigen recognition. Crystal structure analysis of the YVL-BR/HLA-A2 complex revealed that the MHC-bound peptide bulges at position 4, exposing a negatively charged aspartic acid that may interact with the positively charged lysine of CDR3alpha. TCR cloning and site-directed mutagenesis of the CDR3alpha lysine ablated YVL-BR-tetramer staining and substantially reduced CD69 upregulation on TCR mutant-transduced cells following antigen-specific stimulation. Reduced activation of T cells expressing this CDR3 motif was also observed following exposure to mutated (D4A) peptide. In summary, we show that a highly public TCR repertoire to an immunodominant epitope of a common human virus is almost completely selected on the basis of CDR3alpha and provide a likely structural basis for the selection. These studies emphasize the importance of examining TCRalpha, as well as TCRbeta, in understanding the CD8 T cell receptor repertoire.
CDR3alpha drives selection of the immunodominant Epstein Barr virus (EBV) BRLF1-specific CD8 T cell receptor repertoire in primary infection.,Kamga L, Gil A, Song I, Brody R, Ghersi D, Aslan N, Stern LJ, Selin LK, Luzuriaga K PLoS Pathog. 2019 Nov 25;15(11):e1008122. doi: 10.1371/journal.ppat.1008122., eCollection 2019 Nov. PMID:31765434[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kamga L, Gil A, Song I, Brody R, Ghersi D, Aslan N, Stern LJ, Selin LK, Luzuriaga K. CDR3alpha drives selection of the immunodominant Epstein Barr virus (EBV) BRLF1-specific CD8 T cell receptor repertoire in primary infection. PLoS Pathog. 2019 Nov 25;15(11):e1008122. doi: 10.1371/journal.ppat.1008122., eCollection 2019 Nov. PMID:31765434 doi:http://dx.doi.org/10.1371/journal.ppat.1008122
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