A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8.
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.
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism; D016827:CD8 Antigens / Q000737:chemistry* / Q000378:metabolism; D002151:Calorimetry; D003593:Cytoplasm / Q000737:chemistry; D019281:Dimerization; D004151:Dipeptides / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D004151:Dipeptides; D010768:Phosphoserine; C038361:leucylleucine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D015032:Zinc