Conformational Model

Abstract

The failure to identify changes in the crystal structure of the T-cell antigen receptor (TCR) alpha/beta ectodomains beyond the ligand-binding complementarity-determining region loops is most probably responsible for conformational changes having been relegated to a second plane as a mechanism of signal transduction. However, there is strong biochemical and spectroscopic evidence that the cytoplasmic tails of the tcr and the B-cell antigen receptor undergo conformational changes upon stimulation. This suggests that in the context of the whole TCR complex, including both the TCRalpha/beta ectodomains and the complete CD3 subunits with their transmembrane and cytoplasmic tails, the conformational change has to be transmitted from the ectodomains to the cytoplasmic rails upon ligand binding. While the mechanism of transmission and the importance of conformational changes in T- and B-cell activation are still being elucidated, there are already functional correlates that establish a link between full T-cell activation and this conformational change.

TCR Nanoclusters as the Framework for Transmission of Conformational Changes and Cooperativity

“…As for other membrane receptors (Risueno et al, 2008b), the mechanism proposed for the transmission of the conformational change across the membrane involves piston-like, rotational, and sliding movements (Kuhns et al, 2006; Risueno et al, 2008b). The paired G beta strands of CD3ε and CD3γ form a rigid rod-like connector that could produce a displacement of the transmembrane helices in a piston-like movement (Sun et al, 2001).…”