An alternative conformation of the T-cell receptor alpha constant region.
Alphabeta T-cell receptors (TcRs) play a central role in cellular immune response. They are members of the Ig superfamily, with extracellular regions of the alpha and beta chains each comprising a V-type domain and a C-type domain. We have determined the ectodomain structure of an alphabeta TcR, which recognizes the autoantigen myelin basic protein. The 2.0-A-resolution structure reveals canonical main-chain conformations for the V(alpha), V(beta), and C(beta) domains, but the C(alpha) domain exhibits a main-chain conformation remarkably different from those previously reported for TcR crystal structures. The global IgC-like fold is maintained, but a piston-like rearrangement between BC and DE beta-turns results in beta-strand slippage. This substantial conformational change may represent a signaling intermediate. Our structure is the first example for the Ig fold of the increasingly recognized concept of "metamorphic proteins."
van Boxel
Gijs I
GI
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, The University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Holmes
Samantha
S
Fugger
Lars
L
Jones
E Yvonne
EY
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry*
D016693:Receptors, Antigen, T-Cell, alpha-beta