2B4S

Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase

Summary for 2B4S

• Entry DOI: 10.2210/pdb2b4s/pdb
• Descriptor: Tyrosine-protein phosphatase, non-receptor type 1, Insulin receptor, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase/transferase, phosphorylation, tyrosine protein kinase, hydrolase-transferase complex
• Biological source: Homo sapiens (human); More
• Cellular location: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P18031; Membrane; Single-pass type I membrane protein: P06213
• Total number of polymer chains: 4
• Total formula weight: 140404.96

Authors

Li, S.,Depetris, R.S.,Barford, D.,Chernoff, J.,Hubbard, S.R. (deposition date: 2005-09-26, release date: 2005-11-15, Last modification date: 2024-11-13)

Primary citation

Li, S.,Depetris, R.S.,Barford, D.,Chernoff, J.,Hubbard, S.R.
Crystal Structure of a Complex between Protein Tyrosine Phosphatase 1B and the Insulin Receptor Tyrosine Kinase.
Structure, 13:1643-1651, 2005

PubMed Abstract: 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 A 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.

PubMed: 16271887
DOI: 10.1016/j.str.2005.07.019

Experimental method

X-RAY DIFFRACTION (2.3 Å)