2YT2

Solution structure of the chimera of the PTB domain of SNT-2 and 19-residue peptide (aa 1571-1589) of hALK

Summary for 2YT2

• Entry DOI: 10.2210/pdb2yt2/pdb
• NMR Information: BMRB: 11095
• Descriptor: Fibroblast growth factor receptor substrate 3 and ALK tyrosine kinase receptor (1 entity in total)
• Functional Keywords: chimera, snt-2, ptb domain, halk, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: Q9UM73
• Total number of polymer chains: 1
• Total formula weight: 16953.82

Authors

Li, H.,Koshiba, S.,Tomizawa, T.,Watanabe, S.,Harada, T.,Kigawa, T.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2007-04-05, release date: 2008-04-08, Last modification date: 2024-05-01)

Primary citation

Koshiba, S.,Li, H.,Motoda, Y.,Tomizawa, T.,Kasai, T.,Tochio, N.,Yabuki, T.,Harada, T.,Watanabe, S.,Tanaka, A.,Shirouzu, M.,Kigawa, T.,Yamamoto, T.,Yokoyama, S.
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.Genom., 11:125-141, 2010

PubMed 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.

PubMed: 20454865
DOI: 10.1007/s10969-010-9091-x

Experimental method

SOLUTION NMR