1lcj
From Proteopedia
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SH2 (SRC HOMOLOGY-2) DOMAIN OF HUMAN P56-LCK TYROSINE KINASE COMPLEXED WITH THE 11 RESIDUE PHOSPHOTYROSYL PEPTIDE EPQPYEEIPIYL
Contents |
Overview
The Src homology-2 (SH2) domains are modules of about 100 amino-acid, residues that are found in many intracellular signal-transduction, proteins. They bind phosphotyrosine-containing sequences with high, affinity and specificity, recognizing phosphotyrosine in the context of, the immediately adjacent polypeptide sequence. The protein p56lck (Lck) is, a Src-like, lymphocyte-specific tyrosine kinase. A phosphopeptide library, screen has recently been used to deduce an 'optimal' binding sequence for, the Lck SH2 domain. There is selectivity for the residues Glu, Glu and Ile, in the three positions C-terminal to the phosphotyrosine. An 11-residue, phosphopeptide derived from the hamster polyoma middle-T antigen, EPQpYEEIPIYL, binds with an approximately 1 nM dissociation constant to, the Lck SH2 (ref. 17), an affinity equivalent to that of the tightest, known SH2-phosphopeptide complex. We report here the high-resolution, crystallographic analysis of the Lck SH2 domain in complex with this, phosphopeptide. Recent crystallographically derived structures of the Src, SH2 domain in complex with low-affinity peptides, which do not contain the, EEI consensus, and NMR-derived structures of unliganded Abl (ref. 19) and, p85 (ref. 20) SH2 domains have revealed the conserved fold of the SH2, domain and the properties of a phosphotyrosine binding pocket. Our, high-affinity complex shows the presence of a second pocket for the, residue (pY + 3) three positions C-terminal to the phosphotyrosine (pY)., The peptide is anchored by insertion of the pY and pY + 3 side chains into, their pockets and by a network of hydrogen bonds to the peptide main, chain. In the low-affinity phosphopeptide/Src complexes, the pY + 3, residues do not insert into the homologous binding pocket and the peptide, main chain remains displaced from the surface of the domain.
Disease
Known disease associated with this structure: SCID due to LCK deficiency OMIM:[153390]
About this Structure
1LCJ is a Protein complex structure of sequences from Homo sapiens with PHS as ligand. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck., Eck MJ, Shoelson SE, Harrison SC, Nature. 1993 Mar 4;362(6415):87-91. PMID:7680435
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