6mrp

Structure of the Bovine p85a BH domain R228E mutantStructure of the Bovine p85a BH domain R228E mutant

Structural highlights 6mrp is a 2 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.403Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function P85A_BOVIN Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity). Publication Abstract from PubMed The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in regulating cell growth and cell survival and is frequently deregulated in cancer cells. p85alpha regulates the p110alpha lipid kinase, and also stabilizes and stimulates PTEN, the lipid phosphatase that downregulates this pathway. In this report, we determined that the p85alpha BH domain binds several phosphorylated phosphoinositide lipids, an interaction that could help localize p85alpha to membranes rich in these lipids. We also identified key residues responsible for mediating PTEN - p85alpha complex formation. Based on these experimental results, a docking model for the PTEN - p85alpha BH domain complex was developed that is consistent with the known binding interactions for both PTEN and p85alpha. This model involves extensive side-chain and peptide backbone contacts between both the PASE and C2 domains of PTEN with the p85alpha BH domains. The p85alpha BH domain residues shown to be important for PTEN binding were p85alpha residues E212, Q221, K225, R228 and H234. We also verified experimentally the importance of PTEN-E91 in mediating the interaction with the p85alpha BH domain. These results shed new light on the mechanism of PTEN regulation by p85alpha. Insight into the PTEN - p85alpha interaction and lipid binding properties of the p85alpha BH domain.,Marshall JDS, Mellor P, Ruan X, Whitecross DE, Moore SA, Anderson DH Oncotarget. 2018 Dec 11;9(97):36975-36992. doi: 10.18632/oncotarget.26432., eCollection 2018 Dec 11. PMID:30651929 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6mrp, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image