A membrane-proximal tetracysteine motif contributes to assembly of CD3δε and CD3γε dimers with the T cell receptor

Abstract

Assembly of the T cell receptor (TCR) with its dimeric signaling modules, CD3δε, CD3γε, and ζζ, is organized by transmembrane (TM) interactions. Each of the three assembly steps requires formation of a three-helix interface involving one particular basic TCR TM residue and two acidic TM residues of the respective signaling dimer. The extracellular domains of CD3δε and CD3γε contribute to assembly, but TCR interaction sites on CD3 dimers have not been defined. The structures of the extracellular domains of CD3δε and CD3γε demonstrated parallel β-strands ending at the first cysteine in the CXXCXEXXX motif present in the stalk segment of each CD3 chain. Mutation of the membrane-proximal cystein..