6mf8

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==TCR alpha transmembrane domain==
==TCR alpha transmembrane domain==
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<StructureSection load='6mf8' size='340' side='right'caption='[[6mf8]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
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<StructureSection load='6mf8' size='340' side='right'caption='[[6mf8]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6mf8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MF8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MF8 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6mf8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MF8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MF8 FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tcra ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<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=6mf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mf8 OCA], [http://pdbe.org/6mf8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mf8 RCSB], [http://www.ebi.ac.uk/pdbsum/6mf8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mf8 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6mf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mf8 OCA], [https://pdbe.org/6mf8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mf8 RCSB], [https://www.ebi.ac.uk/pdbsum/6mf8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mf8 ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/TRAC_MOUSE TRAC_MOUSE] Constant region of T cell receptor (TR) alpha chain. 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. 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. 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.[UniProtKB:P01848]
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Initial molecular details of cellular activation following alphabetaT cell antigen receptor (TCR) ligation by peptide-major histocompatibility complexes (pMHC) remain unexplored. We determined the nuclear magnetic resonance (NMR) structure of the TCRalpha subunit transmembrane (TM) domain revealing a bipartite helix whose segmentation fosters dynamic movement. Positively charged TM residues Arg251 and Lys256 project from opposite faces of the helix, with Lys256 controlling immersion depth. Their modification caused stepwise reduction in TCR associations with CD3zetazeta homodimers and CD3epsilongamma plus CD3epsilondelta heterodimers, respectively, leading to an activated transcriptome. Optical tweezers revealed that Arg251 and Lys256 mutations altered alphabetaTCR-pMHC bond lifetimes, while mutations within interacting TCRalpha connecting peptide and CD3delta CxxC motif juxtamembrane elements selectively attenuated signal transduction. Our findings suggest that mechanical forces applied during pMHC ligation initiate T cell activation via a dissociative mechanism, shifting disposition of those basic sidechains to rearrange TCR complex membrane topology and weaken TCRalphabeta and CD3 associations.
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The T Cell Antigen Receptor alpha Transmembrane Domain Coordinates Triggering through Regulation of Bilayer Immersion and CD3 Subunit Associations.,Brazin KN, Mallis RJ, Boeszoermenyi A, Feng Y, Yoshizawa A, Reche PA, Kaur P, Bi K, Hussey RE, Duke-Cohan JS, Song L, Wagner G, Arthanari H, Lang MJ, Reinherz EL Immunity. 2018 Nov 20;49(5):829-841.e6. doi: 10.1016/j.immuni.2018.09.007. Epub, 2018 Oct 30. PMID:30389415<ref>PMID:30389415</ref>
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==See Also==
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*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6mf8" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Lk3 transgenic mice]]
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[[Category: Mus musculus]]
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[[Category: Brazin, K N]]
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[[Category: Brazin KN]]
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[[Category: Reinherz, E L]]
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[[Category: Reinherz EL]]
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[[Category: Immune system]]
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[[Category: Mechanoreceptor]]
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[[Category: Tcr]]
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[[Category: Transmembrane]]
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Current revision

TCR alpha transmembrane domain

PDB ID 6mf8

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