PDBsum entry 2kup

Signaling protein/oncoprotein

PDB id: 2kup

Contents

Protein chains

146 a.a. *

19 a.a. *

* Residue conservation analysis

PDB id:

2kup

Name:

Signaling protein/oncoprotein

Title:

Solution structure of the complex of the ptb domain of snt-2 and 19- residue peptide (aa 1571-1589) of halk

Structure:

Fibroblast growth factor receptor substrate 3. Chain: a. Fragment: ptb domain. Synonym: fgfr substrate 3, suc1-associated neurotrophic factor target 2, snt-2, fgfr-signaling adaptor snt2. Engineered: yes. 19-residue peptide from alk tyrosine kinase receptor. Chain: b. Synonym: halk, anaplastic lymphoma kinase.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cell-free synthesis. Synthetic: yes. Other_details: chemically synthesized

NMR struc:

20 models

Authors:

H.Li,S.Koshiba,M.Inoue,T.Kigawa,S.Yokoyama,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

Date:

24-Feb-10 Release date: 26-May-10

Protein chain

O43559  (FRS3_HUMAN) -  Fibroblast growth factor receptor substrate 3 from Homo sapiens

Seq: 492 a.a.

Struc: 146 a.a.*

Protein chain

Q9UM73  (ALK_HUMAN) -  ALK tyrosine kinase receptor from Homo sapiens

Seq: 1620 a.a.

Struc: 19 a.a.

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain A: E.C.?
• Enzyme class 3: Chain B: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

Added reference

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.