Phosphorylation of T cell receptor zeta is regulated by a lipid dependent folding transition

The cytoplasmic domain of the T cell receptor zeta subunit (zeta (cyt)) is sufficient to couple receptor ligation to intracellular signaling cascades, but little is known about its structure or mechanism of signaling. In aque ous solution, zeta (cyt), is unstructured. Here we report that in the prese nce of Lipid vesicles zeta (cyt) assumes a folded structure, The folding tr ansition is reversible and dependent on the presence of acidic phospholipid s. In the lipid-bound conformation, zeta (cyt) is refractory to phosphoryla tion by src family tyrosine kinases, which are believed to play a key role in signal initiation in vivo. In the lipid-free, unstructured form, zeta (c yt) is readily phosphorylated, and phospho-zeta (cyt) exhibits neither memb rane association nor structure induction. The conformational change may pro vide a mechanism for coupling receptor clustering to cytoplasmic signaling events.