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Science 13 August 1999:
Vol. 285. no. 5430, pp. 1077 - 1080
DOI: 10.1126/science.285.5430.1077
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Reports

Quaternary Structure of the Insulin-Insulin Receptor Complex

Robert Z.-T. Luo, 1 Daniel R. Beniac, 2 Allan Fernandes, 2 Cecil C. Yip, 1* F. P. Ottensmeyer 2*

The three-dimensional (3D) structure of the intrinsically dimeric insulin receptor bound to its ligand, insulin, was determined by electron cryomicroscopy. Gold-labeled insulin served to locate the insulin-binding domain. The 3D structure was then fitted with available known high-resolution domain substructures to obtain a detailed contiguous model for this heterotetrameric transmembrane receptor. The 3D reconstruction indicates that the two alpha  subunits jointly participate in insulin binding and that the kinase domains in the two beta  subunits are in a juxtaposition that permits autophosphorylation of tyrosine residues in the first step of insulin receptor activation.

1 Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, M5G 1L6, Canada.
2 Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 2M9, Canada.
*   To whom correspondence should be addressed. E-mail: cecil.yip{at}utoronto.ca and fpo{at}oci.utoronto.ca.

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