Crystal Structure of a Complex Between Protein Tyrosine Phosphatase 1B and the Insulin Receptor Tyrosine Kinase

Journal Article · Sat Jan 01 04:00:00 EST 2005 · Structure

DOI:https://doi.org/10.1016/j.str.2005.07.019· OSTI ID:913872

Li, S; Depetris, R; Barford, D; Chernoff, J; Hubbard, S

Protein tyrosine phosphatase 1B (PTP1B) is a highly specific negative regulator of insulin receptor signaling in vivo. The determinants of PTP1B specificity for the insulin receptor versus other receptor tyrosine kinases are largely unknown. Here, we report a crystal structure at 2.3 Angstroms resolution of the catalytic domain of PTP1B (trapping mutant) in complex with the phosphorylated tyrosine kinase domain of the insulin receptor (IRK). The crystallographic asymmetric unit contains two PTP1B-IRK complexes that interact through an IRK dimer interface. Rather than binding to a phosphotyrosine in the IRK activation loop, PTP1B binds instead to the opposite side of the kinase domain, with the phosphorylated activation loops sequestered within the IRK dimer. The crystal structure provides evidence for a noncatalytic mode of interaction between PTP1B and IRK, which could be important for the selective recruitment of PTP1B to the insulin receptor.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 913872
• Report Number(s): BNL--78440-2007-JA
• Journal Information: Structure, Journal Name: Structure Journal Issue: 11 Vol. 13
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DIMERS
IN VIVO
INSULIN
PHOSPHATASES
PHOSPHOTRANSFERASES
PROTEINS
RESOLUTION
SPECIFICITY
TRAPPING
TYROSINE
national synchrotron light source