1FU6

NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE

Summary for 1FU6

• Entry DOI: 10.2210/pdb1fu6/pdb
• Related: 1FU5
• Descriptor: PHOSPHATIDYLINOSITOL 3-KINASE REGULATORY ALPHA SUBUNIT (1 entity in total)
• Functional Keywords: central beta-sheet with two flanking alpha-helices, protein binding
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 1
• Total formula weight: 12870.38

Authors

Weber, T.,Schaffhausen, B.,Liu, Y.,Guenther, U.L. (deposition date: 2000-09-14, release date: 2001-02-21, Last modification date: 2024-05-22)

Primary citation

Weber, T.,Schaffhausen, B.,Liu, Y.,Gunther, U.L.
NMR structure of the N-SH2 of the p85 subunit of phosphoinositide 3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosine binding site.
Biochemistry, 39:15860-15869, 2000

PubMed Abstract: The N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K) has a higher affinity for a peptide with two phosphotyrosines than for the same peptide with only one. This unexpected result was not observed for the C-terminal SH2 from the same protein. NMR structural analysis has been used to understand the behavior of the N-SH2. The structure of the free SH2 domain has been compared to that of the SH2 complexed with a doubly phosphorylated peptide derived from polyomavirus middle T antigen (MT). The structure of the free SH2 domain shows some differences from previous NMR and X-ray structures. In the N-SH2 complexed with a doubly phosphorylated peptide, a second site for phosphotyrosine interaction has been identified. Further, line shapes of NMR signals showed that the SH2 protein-ligand complex is subject to temperature-dependent conformational mobility. Conformational mobility is also supported by the spectra of the ligand peptide. A binding model which accounts for these results is developed.

PubMed: 11123912
DOI: 10.1021/bi001474d

Experimental method

SOLUTION NMR