1P5T

Crystal Structure of Dok1 PTB Domain

1P5T の概要

• エントリーDOI: 10.2210/pdb1p5t/pdb
• 分子名称: Docking protein 1 (2 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cytoplasm (By similarity): P97465
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28934.00

構造登録者

Shi, N.,Ye, S.,Liu, Y.,Zhou, W.,Ding, Y.,Lou, Z.,Qiang, B.,Yuan, J.,Rao, Z. (登録日: 2003-04-28, 公開日: 2004-02-17, 最終更新日: 2024-10-16)

主引用文献

Shi, N.,Ye, S.,Bartlam, M.,Yang, M.,Wu, J.,Liu, Y.,Sun, F.,Han, X.,Peng, X.,Qiang, B.,Yuan, J.,Rao, Z.
Structural Basis for the Specific Recognition of RET by the Dok1 Phosphotyrosine Binding Domain
J.BIOL.CHEM., 279:4962-4969, 2004

PubMed Abstract: 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.

PubMed: 14607833
DOI: 10.1074/jbc.M311030200

実験手法

X-RAY DIFFRACTION (2.35 Å)