Crystal structure of an isolated Vα domain of the 2C T-cell receptor

The T-cell receptor (TCR) is a heterodimeric cell-surface protein consisting of two chains, alpha and beta, each of which is composed of a variable (V) and a constant (C) domain. Crystals of the isolated V-alpha domain of the murine TCR 2C were grown by serendipity from a solution containing the extracellular domains of the intact TCR 2C and CD3 gamma epsilon -chains. The V-alpha crystal structure shows how crystal packing can substitute for another V-alpha domain in a different fashion from that observed in V-alpha/V-beta homodimer and V-alpha/V-beta heterodimer structures. Significant conformational changes occur in the CDR3 and beta (3)beta (4) loops that normally form part of the dimer interface. The monomeric V-alpha domain provides the unique opportunity to study the effect of dimerization on the conformation of the unliganded complementarity-determining regions (CDR) of a TCR. This structure of an individual V-alpha module has implications for stability and bioengineering of isolated antibody and immunoglobulin domains. (C) 2001 Academic Press.