1uef
Crystal Structure of Dok1 PTB Domain Complex
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OverviewOverview
Dok1 is a common substrate of activated protein-tyrosine kinases. It is, rapidly tyrosine-phosphorylated in response to receptor tyrosine, activation and interacts with ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun, N-terminal kinase (JNK) and c-Jun activation, respectively. In chronic, myelogenous leukemia cells, it has shown constitutive phosphorylation. The, N-terminal phosphotyrosine binding (PTB) domain of Dok1 can recognize and, bind specifically to phosphotyrosine-containing motifs of receptors. Here, we report the crystal structure of the Dok1 PTB domain alone and in, complex with a phosphopeptide derived from RET receptor tyrosine kinase., The structure consists of a beta-sandwich composed of two nearly, orthogonal, 7-stranded, antiparallel beta-sheets, and it is capped at one, side by a C-terminal alpha-helix. The RET phosphopeptide binds to Dok1 via, a surface groove formed between strand beta5 and the C-terminal, alpha-helix of the PTB domain. The structures reveal the molecular basis, for the specific recognition of RET by the Dok1 PTB domain. We also show, that Dok1 does not recognize peptide sequences from TrkA and IL-4, which, are recognized by Shc and IRS1, respectively.
About this StructureAbout this Structure
1UEF is a Protein complex structure of sequences from Mus musculus with PO3 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.
ReferenceReference
Structural basis for the specific recognition of RET by the Dok1 phosphotyrosine binding domain., Shi N, Ye S, Bartlam M, Yang M, Wu J, Liu Y, Sun F, Han X, Peng X, Qiang B, Yuan J, Rao Z, J Biol Chem. 2004 Feb 6;279(6):4962-9. Epub 2003 Nov 7. PMID:14607833
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