Publication Date:
2003-09-23
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Peter W -- Sun, Zhen-Yu J -- Blacklow, Stephen C -- Wagner, Gerhard -- Eck, Michael J -- CA080942/CA/NCI NIH HHS/ -- HL61001/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Sep 19;301(5640):1725-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14500983" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Motifs
;
Amino Acid Sequence
;
Animals
;
Antigens, CD4/*chemistry/metabolism
;
Antigens, CD8/*chemistry/metabolism
;
Calorimetry
;
Cytoplasm/chemistry
;
Dimerization
;
Dipeptides/chemistry
;
Humans
;
Hydrophobic and Hydrophilic Interactions
;
Lymphocyte Activation
;
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/*chemistry/metabolism
;
Models, Molecular
;
Molecular Sequence Data
;
Nuclear Magnetic Resonance, Biomolecular
;
Phosphorylation
;
Phosphoserine/metabolism
;
Protein Conformation
;
Protein Folding
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Sequence Alignment
;
T-Lymphocytes/immunology/physiology
;
Zinc/*chemistry/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
