Download MendeleyNMR 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.
Weber, T., Schaffhausen, B., Liu, Y., Gunther, U.L.(2000) Biochemistry 39: 15860-15869
- PubMed: 11123912
- DOI: https://doi.org/10.1021/bi001474d
- Primary Citation of Related Structures:
1FU5, 1FU6 - 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.
Organizational Affiliation:
Institut f¨¹r Biophysikalische Chemie, J. W. Goethe Universit?t, Frankfurt, Biozentrum N230, Marie-Curie-Strasse 9, 60439 Frankfurt, Germany.
