6MF8

TCR alpha transmembrane domain

Summary for 6MF8

• Entry DOI: 10.2210/pdb6mf8/pdb
• NMR Information: BMRB: 30513
• Descriptor: T-cell receptor alpha chain C region (1 entity in total)
• Functional Keywords: mechanoreceptor, transmembrane, tcr, immune system
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 5250.16

Authors

Brazin, K.N.,Reinherz, E.L. (deposition date: 2018-09-10, release date: 2018-12-12, Last modification date: 2024-05-01)

Primary citation

Brazin, K.N.,Mallis, R.J.,Boeszoermenyi, A.,Feng, Y.,Yoshizawa, A.,Reche, P.A.,Kaur, P.,Bi, K.,Hussey, R.E.,Duke-Cohan, J.S.,Song, L.,Wagner, G.,Arthanari, H.,Lang, M.J.,Reinherz, E.L.
The T Cell Antigen Receptor alpha Transmembrane Domain Coordinates Triggering through Regulation of Bilayer Immersion and CD3 Subunit Associations.
Immunity, 49:829-841.e6, 2018

PubMed Abstract: Initial molecular details of cellular activation following αβT cell antigen receptor (TCR) ligation by peptide-major histocompatibility complexes (pMHC) remain unexplored. We determined the nuclear magnetic resonance (NMR) structure of the TCRα 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 CD3ζζ homodimers and CD3εγ plus CD3εδ heterodimers, respectively, leading to an activated transcriptome. Optical tweezers revealed that Arg251 and Lys256 mutations altered αβTCR-pMHC bond lifetimes, while mutations within interacting TCRα connecting peptide and CD3δ 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 TCRαβ and CD3 associations.

PubMed: 30389415
DOI: 10.1016/j.immuni.2018.09.007

Experimental method

SOLUTION NMR