The three-dimensional structure of a T-cell antigen receptor V alpha V beta heterodimer reveals a novel arrangement of the V beta domain.
The crystal structure of a mouse T-cell antigen receptor (TCR) Fv fragment complexed to the Fab fragment of a specific anti-clonotypic antibody has been determined to 2.6 A resolution. The polypeptide backbone of the TCR V alpha domain is very similar to those of other crystallographically determined V alphas, whereas the V beta structure is so far unique among TCR V beta domains in that it displays a switch of the c" strand from the inner to the outer beta-sheet. The beta chain variable region of this TCR antigen-binding site is characterized by a rather elongated third complementarity-determining region (CDR3beta) that packs tightly against the CDR3 loop of the alpha chain, without leaving any intervening hydrophobic pocket. Thus, the conformation of the CDR loops with the highest potential diversity distinguishes the structure of this TCR antigen-binding site from those for which crystallographic data are available. On the basis of all these results, we infer that a significant conformational change of the CDR3beta loop found in our TCR is required for binding to its cognate peptide-MHC ligand.
Housset
D
D
Laboratoire de Cristallographie et Cristallogénèse des Protéines, Institut de Biologie Structurale Jean-Pierre Ebel CEA-CNRS, Grenoble, France.
Mazza
G
G
Grégoire
C
C
Piras
C
C
Malissen
B
B
Fontecilla-Camps
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D019281:Dimerization; D006183:H-2 Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006860:Hydrogen Bonding; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry*
D000941:Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta