1UEF

Crystal Structure of Dok1 PTB Domain Complex

Summary for 1UEF

• Entry DOI: 10.2210/pdb1uef/pdb
• Descriptor: Docking protein 1, 13-mer peptide from Proto-oncogene tyrosine-protein kinase receptor ret (3 entities in total)
• Functional Keywords: protein binding, transferase, phosphotyrosine binding domain, protein binding-transferase complex, protein binding/transferase
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cytoplasm (By similarity): P97465; Membrane; Single-pass type I membrane protein: P35546
• Total number of polymer chains: 4
• Total formula weight: 31995.79

Authors

Shi, N.,Ye, S.,Liu, Y.,Zhou, W.,Ding, Y.,Lou, Z.,Qiang, B.,Yan, J.,Rao, Z. (deposition date: 2003-05-14, release date: 2004-05-25, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)