The structure of the ζζ transmembrane dimer reveals features essential for its assembly with the T cell receptor

The T cell receptor (TCR) alpha beta heterodimer communicates ligand binding to the cell interior via noncovalently associated CD3 gamma epsilon, CD3 delta epsilon, and xi xi dimers. While structures of extracellular components of the TCR-CD3 complex are known, the transmembrane (TM) domains that mediate assembly have eluded structural characterization. Incorporation of the xi xi signaling module is known to require one basic TCR alpha and two xi xi aspartic acid TM residues. We report the NMR structure of the xi xi(TM) dinner, a left-handed coiled coil with substantial polar contacts. Mutagenesis experiments demonstrate that three polar positions are critical for xi xi dimerization and assembly with TCR. The two aspartic acids create a single structural unit at the a interface stabilized by extensive hydrogen bonding, and there is evidence for a structural water molecule (or molecules) within close proximity. This structural unit, representing only the second transmembrane dinner interface solved to date, serves as a paradigm for the assembly of all modules involved in TCR signaling.