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Science 301 (5640): 1725-1728

Copyright © 2003 by the American Association for the Advancement of Science

A Zinc Clasp Structure Tethers Lck to T Cell Coreceptors CD4 and CD8

Peter W. Kim,1,2 Zhen-Yu J. Sun,2 Stephen C. Blacklow,3 Gerhard Wagner,2 Michael J. Eck1,2*

Abstract: The T cell coreceptors CD4 and CD8 both associate via their cytoplasmic tails with the N-terminus of the Src-family tyrosine kinase Lck. These interactions require zinc and are critical for T cell development and activation. We examined the folding and solution structures of ternary CD4-Lck-Zn2+ and CD8{alpha}-Lck-Zn2+ complexes. The coreceptor tails and the Lck N-terminus are unstructured in isolation but assemble in the presence of zinc to form compactly folded heterodimeric domains. The cofolded complexes have similar "zinc clasp" cores that are augmented by distinct structural elements. A dileucine motif required for clathrin-mediated endocytosis of CD4 is masked by Lck.

1 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
3 Brigham and Women's Hospital and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: eck{at}red.dfci.harvard.edu


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