View source for 5xot


==Crystal structure of pHLA-B35 in complex with TU55 T cell receptor==
<StructureSection load='5xot' size='340' side='right'caption='[[5xot]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xot]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XOT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.787&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5xot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xot OCA], [https://pdbe.org/5xot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xot RCSB], [https://www.ebi.ac.uk/pdbsum/5xot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xot ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[https://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 ==
[https://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 ==
Given a limited set of TCR V genes which are used to create TCRs that are reactive to different ligands, such as MHC class I, MHC class II and MHC-like proteins (for example, MIC molecules and CD1 molecules), the Vdelta1 segment can be rearranged with Ddelta-Jdelta-Cdelta or Jalpha-Calpha segments, to form classical gammadeltaTCR or uncommon alphabetaTCR using a Vdelta1 segment (delta/alphabetaTCR). Here we have determined two complex structures of the delta/alphabetaTCRs (S19-2 and TU55) bound to different locus-disparate MHCIs with HIV peptides (HLA-A*2402-Nef138-10 and HLA-B*3501-Pol448-9). The overall binding modes resemble classical alphabetaTCRs, but display a strong tilt binding geometry of Vdelta1 domain towards the HLA alpha1 helix, due to a conserved extensive interaction between the CDR1delta loop and N-terminal region of alpha1 helix (mainly in position 62). The aromatic amino acids of the CDR1delta loop exploit different conformations ("aromatic-ladder" or "aromatic-hairpin") to accommodate distinct MHC helical scaffolds. This tolerance helps to explain how a particular TCR V region can similarly dock onto multiple MHC molecules, and thus, may potentially explain the nature of TCR cross-reactivity. In addition, the length of CDR3delta loop could affect the extent of tilt binding of Vdelta1 domain, and adaptively, the pairing Vbeta domains adjust their mass centers to generate differential MHC contacts, hence probably ensuring the TCR specificity to a certain peptide-MHC. Our data have provided further structural insights into the TCR recognition of classical pMHCI molecules, unifying the cross-reactivity and specificity together.IMPORTANCE The specificity of alphabeta T cell recognition is determined by the CDR loops of the alphabetaTCR and the general binding mode of alphabetaTCRs to pMHC has been established over the last decade. Due to the intrinsic genomic structure of the TCR alpha/delta chain locus, some Vdelta segments can rearrange with Calpha segment, forming a hybrid VdeltaCalphaVbetaCbeta TCR, delta/alphabetaTCR. However, the basis for the molecular recognition of such TCRs to their ligands is elusive. Here, an alphabetaTCR using Vdelta1 segment, S19-2, is isolated from a HIV-infected patient, in an HLA-A*24:02 restricted manner. Then we solved the crystal structures of S19-2 TCR and another delta/alphabetaTCR TU55 binding to their ligands respectively, revealing a conserved Vdelta1 binding feature. Further binding kinetics analysis reveals that the S19-2 and TU55 TCRs bind pHLA very tightly and long-lastingly. Our results illustrate the binding mode of a TCR using Vdelta1 segment to its ligand, virus-derived pHLA.

Conserved Vdelta1 binding geometry in a setting of locus-disparate pHLA recognition by delta/alphabetaTCRs: insight into recognition of HIV peptides by TCR.,Shi Y, Kawana-Tachikawa A, Gao F, Qi J, Liu C, Gao J, Cheng H, Ueno T, Iwamoto A, Gao GF J Virol. 2017 Jun 14. pii: JVI.00725-17. doi: 10.1128/JVI.00725-17. PMID:28615212<ref>PMID:28615212</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xot" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Gao GF]]
[[Category: Qi J]]
[[Category: Shi Y]]