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A Zinc Clasp Structure Tethers Lck to T Cell Coreceptors CD4 and CD8
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-Zn 2 + and CD8α-Lck-Zn 2 + 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.
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Cited by
Bidirectional Transmembrane Signaling by Cytoplasmic Domain Separation in Integrins
Kim, M., Carman, C. V., & Springer, T. A. (2003) · Science · doi:10.1126/science.1084174 · Cited by 786
Structure and regulation of Src family kinases
Boggon, T. J., & Eck, M. J. (2004) · Oncogene · doi:10.1038/sj.onc.1208081 · Cited by 712
Self-citationIon channels and transporters in lymphocyte function and immunity
Feske, S., Skolnik, E. Y., & Prakriya, M. (2012) · Nature Reviews Immunology · doi:10.1038/nri3233 · Cited by 441
The immune system and the impact of zinc during aging
Haase, H., & Rink, L. (2009) · Immunity & Ageing · doi:10.1186/1742-4933-6-9 · Cited by 334
Maywald, M., Wessels, I., & Rink, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102222 · Cited by 309
Metadata
- Authors
- Kim, P. W., Sun, Z.-Y. J., Blacklow, S. C., Wagner, G., & Eck, M. J.
- Venue
- Science
- Published
- 2003-09-19
- Volume
- 301
- Issue
- 5640
- Pages
- 1725-1728
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2072659663
- Cited by
- 276
- References
- 0
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- closed
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- Kim, P. W., Sun, Z.-Y. J., Blacklow, S. C., Wagner, G., & Eck, M. J. (2003). A Zinc Clasp Structure Tethers Lck to T Cell Coreceptors CD4 and CD8. Science. https://doi.org/10.1126/science.1085643
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