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

Abstract

The T-cell receptor (TCR) is a heterodimeric cell-surface protein consisting of two chains, α and β, each of which is composed of a variable (V) and a constant (C) domain. Crystals of the isolated V α domain of the murine TCR 2C were grown by serendipity from a solution containing the extracellular domains of the intact TCR 2C and CD3 γϵ-chains. The V α crystal structure shows how crystal packing can substitute for another V α domain in a different fashion from that observed in V α/V α homodimer and V α/V β heterodimer structures. Significant conformational changes occur in the CDR3 and β 3β 4 loops that normally form part of the dimer interface. The monomeric V α 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 α module has implications for stability and bioengineering of isolated antibody and immunoglobulin domains.