Abstract
The cytoplasmic domain of the T cell receptor ζ subunit (ζcyt) is sufficient to couple receptor ligation to intracellular signaling cascades, but little is known about its structure or mechanism of signaling. In aqueous solution, ζcyt is unstructured. Here we report that in the presence of lipid vesicles ζcyt assumes a folded structure. The folding transition is reversible and dependent on the presence of acidic phospholipids. In the lipid-bound conformation, ζcyt is refractory to phosphorylation by src family tyrosine kinases, which are believed to play a key role in signal initiation in vivo. In the lipid-free, unstructured form, ζcyt is readily phosphorylated, and phospho-ζcyt exhibits neither membrane association nor structure induction. The conformational change may provide a mechanism for coupling receptor clustering to cytoplasmic signaling events.
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Acknowledgements
We thank W. Weissenhorn, S. Harrison and M. Eck for materials. This work was supported by a Career Development Award from the National Science Foundation (L.J.S.), a grant from the National Center for Research Resources for purchase of the BIAcore instrument, and a training grant from the NIH (D.A.).
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Aivazian, D., Stern, L. Phosphorylation of T cell receptor ζ is regulated by a lipid dependent folding transition. Nat Struct Mol Biol 7, 1023–1026 (2000). https://doi.org/10.1038/80930
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DOI: https://doi.org/10.1038/80930
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