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| <StructureSection load='5w1v' size='340' side='right'caption='[[5w1v]], [[Resolution|resolution]] 3.31Å' scene=''> | | <StructureSection load='5w1v' size='340' side='right'caption='[[5w1v]], [[Resolution|resolution]] 3.31Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[5w1v]] is a 20 chain structure with sequence from [http://en.wikipedia.org/wiki/Hcmva Hcmva] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W1V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w1v]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_herpesvirus_5_strain_AD169 Human herpesvirus 5 strain AD169]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W1V FirstGlance]. <br> |
- | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5w1w|5w1w]]</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]] 3.31Å</td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-E, HLA-6.2, HLAE ([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]), UL40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10360 HCMVA]), TRAC TCRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TRBC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5w1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1v OCA], [https://pdbe.org/5w1v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w1v RCSB], [https://www.ebi.ac.uk/pdbsum/5w1v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1v ProSAT]</span></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=5w1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1v OCA], [http://pdbe.org/5w1v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w1v RCSB], [http://www.ebi.ac.uk/pdbsum/5w1v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1v 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/HLAE_HUMAN HLAE_HUMAN]] Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules. [[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. | + | [https://www.uniprot.org/uniprot/HLAE_HUMAN HLAE_HUMAN] Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules. |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| ==See Also== | | ==See Also== |
| *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
- | *[[T-cell receptor|T-cell receptor]] | + | *[[T-cell receptor 3D structures|T-cell receptor 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Hcmva]] | + | [[Category: Homo sapiens]] |
- | [[Category: Human]] | + | [[Category: Human herpesvirus 5 strain AD169]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Farenc, C]] | + | [[Category: Farenc C]] |
- | [[Category: Gras, S]] | + | [[Category: Gras S]] |
- | [[Category: Rossjohn, J]] | + | [[Category: Rossjohn J]] |
- | [[Category: Walpole, N]] | + | [[Category: Walpole N]] |
- | [[Category: Cmv]]
| + | |
- | [[Category: Hla-e]]
| + | |
- | [[Category: Immune system]]
| + | |
- | [[Category: Pmhc-tcr complex]]
| + | |
- | [[Category: T-cell receptor]]
| + | |
- | [[Category: Tcr]]
| + | |
| Structural highlights
Function
HLAE_HUMAN Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules.
Publication Abstract from PubMed
alphabeta T cell receptors (TCRs) interact with peptides bound to the polymorphic Major Histocompatibility Complex class Ia (MHC-Ia) and class II (MHC-II) molecules, as well as the essentially monomorphic MHC class Ib (MHC-Ib) molecules. While there is a large amount of information on how TCRs engage with MHC-Ia and MHC-II, our understanding of TCR-MHC-Ib interactions is very limited. Infection with cytomegalovirus (CMV) can elicit a CD8+ T cell response restricted by the human MHC-Ib molecule, Human Leukocyte Antigen (HLA)-E, and specific for an epitope from UL40 (VMAPRTLIL), which is characterized by biased TRBV14 gene usage. Here we describe an HLA-E-restricted CD8+ T cell able to recognize an allotypic variant of the UL40 peptide, with a modification at position 8 (P8) of the peptide (VMAPRTLVL) that uses the TRBV9 gene segment. We report the structures of a TRBV9+ TCR in complex with the HLA-E molecule presenting the two peptides. Our data revealed that the TRBV9+ TCR adopts a different docking mode and molecular footprint atop HLA-E when compared with the TRBV14+ TCR-HLA-E ternary complex. Additionally, despite their differing V gene segment usage and different docking mechanisms, mutational analyses showed that the TCRs shared a conserved energetic footprint on the HLA-E molecule, focussed around the peptide-binding groove. Hence, we provide new insights into how monomorphic MHC molecules interact with T cells.
A conserved energetic footprint underpins recognition of Human Leukocyte Antigen-E by two distinct alphabeta T cell receptors.,Sullivan LC, Walpole NG, Farenc C, Pietra G, Sum MJW, Clements CS, Lee EJ, Beddoe T, Falco M, Mingari MC, Moretta L, Gras S, Rossjohn J, Brooks AG J Biol Chem. 2017 Sep 25. pii: jbc.M117.807719. doi: 10.1074/jbc.M117.807719. PMID:28972140[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sullivan LC, Walpole NG, Farenc C, Pietra G, Sum MJW, Clements CS, Lee EJ, Beddoe T, Falco M, Mingari MC, Moretta L, Gras S, Rossjohn J, Brooks AG. A conserved energetic footprint underpins recognition of Human Leukocyte Antigen-E by two distinct alphabeta T cell receptors. J Biol Chem. 2017 Sep 25. pii: jbc.M117.807719. doi: 10.1074/jbc.M117.807719. PMID:28972140 doi:http://dx.doi.org/10.1074/jbc.M117.807719
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