PHOSPHATIDYLINOSITOL 3-KINASE, P85-ALPHA SUBUNIT: C-TERMINAL SH2 DOMAIN COMPLEXED WITH A TYR751 PHOSPHOPEPTIDE FROM THE PDGF RECEPTOR, NMR, MINIMIZED MEAN STRUCTURE
Publication Abstract from PubMed
We have determined the solution structure of the C-terminal SH2 domain of the p85 alpha subunit of human phosphatidylinositol (PI) 3-kinase (EC 18.104.22.168) in complex with a phosphorylated tyrosine pentapeptide sequence from the platelet-derived growth factor receptor using heteronuclear nuclear magnetic resonance spectroscopy. Overall, the structure is similar to other SH2 domain complexes, but displays different detail interactions within the phosphotyrosine binding site and in the recognition site for the +3 methionine residue of the peptide, the side chain of which inserts into a particularly deep and narrow pocket which is displaced relative to that of other SH2 domains. The contacts made within this +3 pocket provide the structural basis for the strong selection for methionine at this position which characterizes the SH2 domains of PI3-kinase. Comparison with spectral and structural features of the uncomplexed domain shows that the long BG loop becomes less mobile in the presence of the bound peptide. In contrast, extreme resonance broadening encountered for most residues in the beta D', beta E and beta F strands and associated connecting loops of the domain in the absence of peptide persists in the complex, implying conformational averaging in this part of the molecule on a microsecond-to-millisecond time scale.
Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase., Breeze AL, Kara BV, Barratt DG, Anderson M, Smith JC, Luke RW, Best JR, Cartlidge SA, EMBO J. 1996 Jul 15;15(14):3579-89. PMID:8670861
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1pic is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.
- Breeze AL, Kara BV, Barratt DG, Anderson M, Smith JC, Luke RW, Best JR, Cartlidge SA. Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase. EMBO J. 1996 Jul 15;15(14):3579-89. PMID:8670861