1q69

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1q69

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Solution structure of T-cell surface glycoprotein CD8 alpha chain and Proto-oncogene tyrosine-protein kinase LCK fragments

Contents

Overview

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 CD8alpha-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.

Disease

Known diseases associated with this structure: CD8 deficiency, familial OMIM:[186910], Megakaryoblastic leukemia, acute OMIM:[606078], SCID due to LCK deficiency OMIM:[153390]

About this Structure

1Q69 is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8., Kim PW, Sun ZY, Blacklow SC, Wagner G, Eck MJ, Science. 2003 Sep 19;301(5640):1725-8. PMID:14500983

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