1p5t
From Proteopedia
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'''Crystal Structure of Dok1 PTB Domain''' | '''Crystal Structure of Dok1 PTB Domain''' | ||
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[[Category: Yuan, J.]] | [[Category: Yuan, J.]] | ||
[[Category: Zhou, W.]] | [[Category: Zhou, W.]] | ||
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Revision as of 01:43, 3 May 2008
Crystal Structure of Dok1 PTB Domain
Overview
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 Structure
1P5T is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 04:43:20 2008
Categories: Mus musculus | Single protein | Ding, Y. | Liu, Y. | Lou, Z. | Qiang, B. | Rao, Z. | Shi, N. | Ye, S. | Yuan, J. | Zhou, W. | Signaling protein