title: A conserved αβ transmembrane interface forms the core of a compact T-cell receptor-CD3 structure within the membrane.
abstract: The T-cell antigen receptor (TCR) is an assembly of eight type I single-pass membrane proteins that occupies a central position in adaptive immunity. Many TCR-triggering models invoke an alteration in receptor complex structure as the initiating event, but both the precise subunit organization and the pathway by which ligand-induced alterations are transferred to the cytoplasmic signaling domains are unknown. Here, we show that the receptor complex transmembrane (TM) domains form an intimately associated eight-helix bundle organized by a specific interhelical TCR TM interface. The salient features of this core structure are absolutely conserved between αβ and γδ TCR sequences and throughout vertebrate evolution, and mutations at key interface residues caused defects in the formation of stable TCRαβ:CD3δε:CD3γε:ζζ complexes. These findings demonstrate that the eight TCR-CD3 subunits form a compact and precisely organized structure within the membrane and provide a structural basis for further investigation of conformationally regulated models of transbilayer TCR signaling.
authors: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
authors: Logesvaran
authors: L
authors: Krshnan
authors: Department of Biological Sciences and Bioengineering Program, Lehigh University, Bethlehem, PA 18015.
authors: Soohyung
authors: S
authors: Park
authors: Department of Biological Sciences and Bioengineering Program, Lehigh University, Bethlehem, PA 18015.
authors: Wonpil
authors: W
authors: Im
authors: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; call@wehi.edu.au.
authors: Melissa J
authors: MJ
authors: Call
authors: Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; call@wehi.edu.au.
authors: Matthew E
authors: ME
authors: Call
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017252:CD3 Complex / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology / Q000648:ultrastructure*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology
chemical_list: D017252:CD3 Complex; D021122:Protein Subunits; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins
keywords: MD simulation; NMR; T-cell receptor; cysteine cross-linking; transmembrane structure