1cv9
NMR STUDY OF ITAM PEPTIDE SUBSTRATE
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OverviewOverview
The immunoreceptor tyrosine-based activation motif (ITAM) plays a central, role in transmembrane signal transduction in hematopoietic cells by, mediating responses leading to proliferation and differentiation. An, initial signaling event following activation of the B cell antigen, receptor is phosphorylation of the CD79a (Ig-alpha) ITAM by Lyn, a Src, family protein-tyrosine kinase. To elucidate the structural basis for, recognition between the ITAM substrate and activated Lyn kinase, the, structure of an ITAM-derived peptide bound to Lyn was determined using, exchange-transferred nuclear Overhauser NMR spectroscopy. The bound, substrate structure has an irregular helix-like character. Docking based, on the NMR data into the active site of the closely related Lck kinase, strongly favors ITAM binding in an orientation similar to binding of, cyclic AMP-dependent protein kinase rather than that of insulin receptor, tyrosine kinase. The model of the complex provides a rationale for, conserved ITAM residues, substrate specificity, and suggests that, substrate binds only the active conformation of the Src family tyrosine, kinase, unlike the ATP cofactor, which can bind the inactive form.
About this StructureAbout this Structure
1CV9 is a Protein complex structure of sequences from [1] with ACE and NH2 as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Substrate recognition by the Lyn protein-tyrosine kinase. NMR structure of the immunoreceptor tyrosine-based activation motif signaling region of the B cell antigen receptor., Gaul BS, Harrison ML, Geahlen RL, Burton RA, Post CB, J Biol Chem. 2000 May 26;275(21):16174-82. PMID:10748115
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