PDBsum entry: 2yt2

Signaling protein

PDB id: 2yt2

Contents

Protein chain

153 a.a. *

* Residue conservation analysis

PDB id:

2yt2

Name:

Signaling protein

Title:

Solution structure of the chimera of the ptb domain of snt-2 residue peptide (aa 1571-1589) of halk

Structure:

Fibroblast growth factor receptor substrate 3 and tyrosine kinase receptor. Chain: a. Fragment: ptb domain and 19-residue peptide. Synonym: fgfr substrate 3, suc1-associated neurotrophic fac 2, snt-2, fgfr-signaling adaptor snt2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: cell-free protein synthesis

NMR struc:

20 models

Authors:

H.Li,S.Koshiba,T.Tomizawa,S.Watanabe,T.Harada,T.Kigawa,S.Yok Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

S.Koshiba et al. (2010). Structural basis for the recognition of nucleophosmin-anaplastic lymphoma kinase oncoprotein by the phosphotyrosine binding domain of Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target-2. J Struct Funct Genomics, 11, 125-141. PubMed id: 20454865 DOI: 10.1007/s10969-010-9091-x

Date:

05-Apr-07 Release date: 08-Apr-08

Protein chain

Q9UM73  (ALK_HUMAN) -  ALK tyrosine kinase receptor

Seq: 1620 a.a.

Struc: 153 a.a.*

* PDB and UniProt seqs differ at 128 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - Receptor protein-tyrosine kinase.
• Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biochemical function: insulin receptor binding (1 term)

reference

DOI no: 10.1007/s10969-010-9091-x

J Struct Funct Genomics 11:125-141 (2010)

PubMed id: 20454865

Structural basis for the recognition of nucleophosmin-anaplastic lymphoma kinase oncoprotein by the phosphotyrosine binding domain of Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target-2.

S.Koshiba, H.Li, Y.Motoda, T.Tomizawa, T.Kasai, N.Tochio, T.Yabuki, T.Harada, S.Watanabe, A.Tanaka, M.Shirouzu, T.Kigawa, T.Yamamoto, S.Yokoyama.

ABSTRACT

The nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) fusion oncoprotein, formed by the t(2;5) chromosomal translocation in anaplastic large-cell lymphomas, has constitutive tyrosine kinase activity and interacts with a number of signaling molecules. One of the interacting partners of NPM-ALK is the adaptor protein, Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT), and mutations that deprive NPM-ALK of all three of the SNT-binding sites significantly reduced the transforming activity. In this study, the interactions of the three binding sites in NPM-ALK with the phosphotyrosine binding (PTB) domain of SNT-2 were analyzed. First, by isothermal titration calorimetry, we found that the phosphorylation-independent binding site in NPM-ALK interacts with the SNT-2 PTB domain more tightly than the phosphorylation-dependent binding sites. Second, the solution structure of the SNT-2 PTB domain in complex with the nonphosphorylated NPM-ALK peptide was determined by nuclear magnetic resonance spectroscopy. The NPM-ALK peptide interacts with the hydrophobic surface of the PTB domain and intermolecularly extends the PTB beta-sheet. This interaction mode is much broader and more extensive than those of the phosphorylation-dependent binding sites. Our results indicate that the higher binding activity of the phosphorylation-independent binding site is caused by additional hydrophobic interactions.