Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1.

ABSTRACT: We have determined the crystal structure at 2.3-A resolution of an amino-terminal segment of human insulin receptor substrate 1 that encompasses its pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. Both domains adopt the canonical seven-stranded beta-sandwich PH domain fold. The domains are closely associated, with a 720-A(2) contact surface buried between them that appears to be stabilized by ionic, hydrophobic, and hydrogen bonding interactions. The nonconserved 46-residue linker between the domains is disordered. The PTB domain peptide binding site is fully exposed on the molecular surface, as is a large cationic patch at the base of the PH domain that is a likely binding site for the head groups of phosphatidylinositol phosphates. Binding assays confirm that phosphat

SUBMITTER: Dhe-Paganon S 

PROVIDER: S-EPMC17524 | biostudies-literature | 1999 Jul

REPOSITORIES: biostudies-literature