1IR3

PHOSPHORYLATED INSULIN RECEPTOR TYROSINE KINASE IN COMPLEX WITH PEPTIDE SUBSTRATE AND ATP ANALOG

Summary for 1IR3

• Entry DOI: 10.2210/pdb1ir3/pdb
• Descriptor: INSULIN RECEPTOR, PEPTIDE SUBSTRATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: tyrosine kinase, signal transduction, phosphotransferase, complex (kinase-peptide substrate-atp analog), enzyme, complex (transferase-substrate), complex (transferase-substrate) complex, complex (transferase/substrate)
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P06213
• Total number of polymer chains: 2
• Total formula weight: 37542.82

Authors

Hubbard, S.R. (deposition date: 1997-09-22, release date: 1998-01-07, Last modification date: 2024-10-23)

Primary citation

Hubbard, S.R.
Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog.
EMBO J., 16:5572-5581, 1997

PubMed Abstract: The crystal structure of the phosphorylated, activated form of the insulin receptor tyrosine kinase in complex with a peptide substrate and an ATP analog has been determined at 1.9 A resolution. The activation loop (A-loop) of the kinase undergoes a major conformational change upon autophosphorylation of Tyr1158, Tyr1162 and Tyr1163 within the loop, resulting in unrestricted access of ATP and protein substrates to the kinase active site. Phosphorylated Tyr1163 (pTyr1163) is the key phosphotyrosine in stabilizing the conformation of the tris-phosphorylated A-loop, whereas pTyr1158 is completely solvent-exposed, suggesting an availability for interaction with downstream signaling proteins. The YMXM-containing peptide substrate binds as a short anti-parallel beta-strand to the C-terminal end of the A-loop, with the methionine side chains occupying two hydrophobic pockets on the C-terminal lobe of the kinase. The structure thus reveals the molecular basis for insulin receptor activation via autophosphorylation, and provides insights into tyrosine kinase substrate specificity and the mechanism of phosphotransfer.

PubMed: 9312016
DOI: 10.1093/emboj/16.18.5572

Experimental method

X-RAY DIFFRACTION (1.9 Å)