Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
A Zinc Clasp Structure Tethers Lck to T Cell Coreceptors CD4 and CD8
Peter W. Kim,1,2Zhen-Yu J. Sun,2Stephen C. Blacklow,3Gerhard Wagner,2Michael J. Eck1,2*
The T cell coreceptors CD4 and CD8 both associate via theircytoplasmic tails with the N-terminus of the Src-family tyrosinekinase Lck. These interactions require zinc and are criticalfor T cell development and activation. We examined the foldingand solution structures of ternary CD4-Lck-Zn2+ and CD8-Lck-Zn2+complexes. The coreceptor tails and the Lck N-terminus are unstructuredin isolation but assemble in the presence of zinc to form compactlyfolded heterodimeric domains. The cofolded complexes have similar"zinc clasp" cores that are augmented by distinct structuralelements. A dileucine motif required for clathrin-mediated endocytosisof 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
Conformational Rearrangement within the Soluble Domains of the CD4 Receptor Is Ligand-specific.
Ashish, I. J. Juncadella, R. Garg, C. D. Boone, J. Anguita, and J. K. Krueger (2008)
J. Biol. Chem.
283, 2761-2772
|Abstract »|Full Text »|PDF »
Coreceptor Signal Strength Regulates Positive Selection but Does Not Determine CD4/CD8 Lineage Choice in a Physiologic In Vivo Model.
B. Erman, A. S. Alag, O. Dahle, F. van Laethem, S. D. Sarafova, T. I. Guinter, S. O. Sharrow, A. Grinberg, P. E. Love, and A. Singer (2006)
J. Immunol.
177, 6613-6625
|Abstract »|Full Text »|PDF »
A CD8/Lck Transgene Is Able to Drive Thymocyte Differentiation.
R. C. Fragoso, S. Pyarajan, H. Y. Irie, and S. J. Burakoff (2006)
J. Immunol.
177, 6007-6017
|Abstract »|Full Text »|PDF »
Apoptosis of Antigen-Specific T Lymphocytes upon the Engagement of CD8 by Soluble HLA Class I Molecules Is Fas Ligand/Fas Mediated: Evidence for the Involvement of p56lck, Calcium Calmodulin Kinase II, and Calcium-Independent Protein Kinase C Signaling Pathways and for NF-{kappa}B and NF-AT Nuclear Translocation.
P. Contini, M. Ghio, A. Merlo, A. Poggi, F. Indiveri, and F. Puppo (2005)
J. Immunol.
175, 7244-7254
|Abstract »|Full Text »|PDF »
Carboxyl-Proximal Regions of Reovirus Nonstructural Protein {micro}NS Necessary and Sufficient for Forming Factory-Like Inclusions.
T. J. Broering, M. M. Arnold, C. L. Miller, J. A. Hurt, P. L. Joyce, and M. L. Nibert (2005)
J. Virol.
79, 6194-6206
|Abstract »|Full Text »|PDF »
-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. 
