5e9d

From Proteopedia

(Difference between revisions)

Current revision

RD-1 Mart-1 High bound to Mart-1 decameric peptide (ELA) in complex with HLA-A2

Structural highlights

5e9d is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.51Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TVB65_HUMAN V region of the variable domain of T cell receptor (TR) beta chain that participates in the antigen recognition (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation (PubMed:23524462). The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity (PubMed:15040585).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Utilizing a diverse binding site, T cell receptors (TCRs) specifically recognize a composite ligand comprised of a foreign peptide and a major histocompatibility complex protein (MHC). To help understand the determinants of TCR specificity, we studied a parental and engineered receptor whose peptide specificity had been switched via molecular evolution. Altered specificity was associated with a significant change in TCR-binding geometry, but this did not impact the ability of the TCR to signal in an antigen-specific manner. The determinants of binding and specificity were distributed among contact and non-contact residues in germline and hypervariable loops, and included disruption of key TCR-MHC interactions that bias alphabeta TCRs toward particular binding modes. Sequence-fitness landscapes identified additional mutations that further enhanced specificity. Our results demonstrate that TCR specificity arises from the distributed action of numerous sites throughout the interface, with significant implications for engineering therapeutic TCRs with novel and functional recognition properties.

An Engineered Switch in T Cell Receptor Specificity Leads to an Unusual but Functional Binding Geometry.,Harris DT, Singh NK, Cai Q, Smith SN, Vander Kooi CW, Procko E, Kranz DM, Baker BM Structure. 2016 May 24. pii: S0969-2126(16)30072-7. doi:, 10.1016/j.str.2016.04.011. PMID:27238970^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Le Nours J, Praveena T, Pellicci DG, Gherardin NA, Ross FJ, Lim RT, Besra GS, Keshipeddy S, Richardson SK, Howell AR, Gras S, Godfrey DI, Rossjohn J, Uldrich AP. Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens. Nat Commun. 2016 Feb 15;7:10570. doi: 10.1038/ncomms10570. PMID:26875526 doi:http://dx.doi.org/10.1038/ncomms10570
↑ Nikolich-Zugich J, Slifka MK, Messaoudi I. The many important facets of T-cell repertoire diversity. Nat Rev Immunol. 2004 Feb;4(2):123-32. doi: 10.1038/nri1292. PMID:15040585 doi:http://dx.doi.org/10.1038/nri1292
↑ Brownlie RJ, Zamoyska R. T cell receptor signalling networks: branched, diversified and bounded. Nat Rev Immunol. 2013 Apr;13(4):257-69. doi: 10.1038/nri3403. PMID:23524462 doi:http://dx.doi.org/10.1038/nri3403
↑ Lefranc MP. Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise of Immunoinformatics. Front Immunol. 2014 Feb 5;5:22. doi: 10.3389/fimmu.2014.00022. eCollection 2014. PMID:24600447 doi:http://dx.doi.org/10.3389/fimmu.2014.00022
↑ Rossjohn J, Gras S, Miles JJ, Turner SJ, Godfrey DI, McCluskey J. T cell antigen receptor recognition of antigen-presenting molecules. Annu Rev Immunol. 2015;33:169-200. doi: 10.1146/annurev-immunol-032414-112334., Epub 2014 Dec 10. PMID:25493333 doi:http://dx.doi.org/10.1146/annurev-immunol-032414-112334
↑ Harris DT, Singh NK, Cai Q, Smith SN, Vander Kooi CW, Procko E, Kranz DM, Baker BM. An Engineered Switch in T Cell Receptor Specificity Leads to an Unusual but Functional Binding Geometry. Structure. 2016 May 24. pii: S0969-2126(16)30072-7. doi:, 10.1016/j.str.2016.04.011. PMID:27238970 doi:http://dx.doi.org/10.1016/j.str.2016.04.011

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e9d"

Categories: Homo sapiens | Large Structures | Baker BM | Singh NK

@@ Line 1: / Line 1: @@
 ==RD-1 Mart-1 High bound to Mart-1 decameric peptide (ELA) in complex with HLA-A2==
-<StructureSection load='5e9d' size='340' side='right' caption='[[5e9d]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
+<StructureSection load='5e9d' size='340' side='right'caption='[[5e9d]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5e9d]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E9D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E9D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5e9d]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E9D FirstGlance]. <br>
-</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=5e9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e9d OCA], [http://pdbe.org/5e9d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e9d RCSB], [http://www.ebi.ac.uk/pdbsum/5e9d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e9d ProSAT]</span></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]] 2.51&#8491;</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=5e9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e9d OCA], [https://pdbe.org/5e9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e9d RCSB], [https://www.ebi.ac.uk/pdbsum/5e9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e9d ProSAT]</span></td></tr>
 </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 ==
-[[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_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.
+[https://www.uniprot.org/uniprot/TVB65_HUMAN TVB65_HUMAN] V region of the variable domain of T cell receptor (TR) beta chain that participates in the antigen recognition (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation (PubMed:23524462). The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity (PubMed:15040585).<ref>PMID:26875526</ref> <ref>PMID:15040585</ref> <ref>PMID:23524462</ref> <ref>PMID:24600447</ref> <ref>PMID:25493333</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 18: @@
 </div>
 <div class="pdbe-citations 5e9d" 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/>
 __TOC__
 </StructureSection>
-[[Category: Baker, B M]]
+[[Category: Homo sapiens]]
-[[Category: Singh, N K]]
+[[Category: Large Structures]]
-[[Category: Protein binding]]
+[[Category: Baker BM]]
-[[Category: Single chain tcr-pmhc complex]]
+[[Category: Singh NK]]

5e9d

From Proteopedia

Current revision

RD-1 Mart-1 High bound to Mart-1 decameric peptide (ELA) in complex with HLA-A2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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