Canonical structures for the hypervariable regions of T cell alphabeta receptors.
T cell alphabeta receptors have binding sites for peptide-MHC complexes formed by six hypervariable regions. Analysis of the six atomic structures known for Valpha and for Vbeta domains shows that their first and second hypervariable regions have one of three or four different main-chain conformations (canonical structures). Six of these canonical structures have the same conformation in complexes with peptide-MHC complexes, the free receptor and/or in an isolated V domain. Thus, for at least the first and second hypervariable regions in the currently known structures, the conformation of the canonical structures is well defined in the free state and is conserved on formation of complexes with peptide-MHC. We identified the key residues that are mainly responsible for the conformation of each canonical structure. The first and second hypervariable regions of Valpha and Vbeta domains are encoded by the germline V segments. Humans have 37 functional Valpha segments and 47 Vbeta segments, and mice have 20 Vbeta segments. Inspection of the size of their hypervariable regions, and of sites that contain key residues, indicates that close to 70 % of Valpha segments and 90 % of Vbeta segments have hypervariable regions with a conformation of one of the known canonical structures. The alpha and beta V gene segments in both humans and mice have only a few combinations of different canonical structure in their first and second hypervariable regions. In human Vbeta domains, the number of different sequences with these canonical structure combinations is larger than in mice, whilst for Valpha domains it is probably smaller.
Al-Lazikani
B
B
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
Lesk
A M
AM
Chothia
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C
D000595:Amino Acid Sequence; D000818:Animals; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D014644:Genetic Variation; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta