PDBsum entry 1p5t

Signaling protein

PDB id: 1p5t

Contents

Protein chains

107 a.a. *

Waters ×16

* Residue conservation analysis

PDB id:

1p5t

Name:

Signaling protein

Title:

Crystal structure of dok1 ptb domain

Structure:

Docking protein 1. Chain: a, b. Fragment: dok1 ptb domain. Synonym: dok1. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: mdok1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PQS)

Resolution:

2.35Å R-factor: 0.218 R-free: 0.265

Authors:

N.Shi,S.Ye,Y.Liu,W.Zhou,Y.Ding,Z.Lou,B.Qiang,J.Yuan,Z.Rao

Key ref:

N.Shi et al. (2004). Structural basis for the specific recognition of RET by the Dok1 phosphotyrosine binding domain. J Biol Chem, 279, 4962-4969. PubMed id: 14607833 DOI: 10.1074/jbc.M311030200

Date:

28-Apr-03 Release date: 17-Feb-04

Protein chains

P97465  (DOK1_MOUSE) -  Docking protein 1 from Mus musculus

Seq: 482 a.a.

Struc: 107 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1074/jbc.M311030200

J Biol Chem 279:4962-4969 (2004)

PubMed id: 14607833

Structural basis for the specific recognition of RET by the Dok1 phosphotyrosine binding domain.

N.Shi, S.Ye, M.Bartlam, M.Yang, J.Wu, Y.Liu, F.Sun, X.Han, X.Peng, B.Qiang, J.Yuan, Z.Rao.

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.

Selected figure(s)

Figure 2.
FIG. 2. Overall structure of dok1 PTB domain. a, ribbon stereo diagram showing the fold of the Dok1 PTB domain (green) and the orientation of the bound RET phosphopeptide (white). The ribbon diagram was generated with the program BOBSCRIPT (11). b, structure-based sequence alignments of the nine Doks and hIRS1 PTB domains. Sequences of mouse Dok1-(147-264), human dok1-(147-264), mouse Dok2-(144-259), human Dok2-(141-257), mouse Dok3-(156-266), mouse Dok4-(133-242), human Dok4-(133-242), mouse Dok5-(134-242), human Dok5-(129-232), and human IRS1-(160-262) were aligned. Numbers refer to mouse Dok1. The conserving residues were boxed in red and blue. Critical arginines for phosphotyrosine recognition are indicated by green dots. Alignment was generated using CLUSTAL X (1.8).

Figure 5.
FIG. 5. Stereo view of the interactions between residues at pY-1 of the phosphopeptide, shown in brown, and Dok1 (a) or IRS1 (b) PTB domain. Residues involved in important interactions are shown in ball-and-stick representation. The residues interacting with pY-1 are represented as green; the sulfur atom is represented in yellow.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 4962-4969) copyright 2004.

Figures were selected by an automated process.