title: Insulin binding changes the interface region between alpha subunits of the insulin receptor.
abstract: The homobifunctional cross-linking reagent disuccinimidyl suberate (DSS) was used to probe the interface region between the two alpha subunits of the alpha 2 beta 2 human insulin receptor. The two alpha subunits formed a covalent dimer when affinity-purified receptor or membrane-bound receptor was reacted with DSS. The alpha 2 species was detected on protein blots from SDS gels using an anti-alpha-subunit antibody or 125I-concanavalin A. Alternatively, iodinated receptor was reacted with DSS and the alpha 2 species measured directly in an SDS gel. As shown by all three assay systems, more alpha 2 was formed when insulin was bound to receptor than when insulin was absent. These data indicate that the conformational change which occurs in the alpha subunit in response to insulin binding results in a change in the alpha-alpha interaction within the receptor complex. The results are consistent with a kinase activation mechanism involving communication between the two alpha beta receptor halves.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
authors.forename: S M
authors.initials: SM
authors.lastname: Waugh
authors.forename: P F
authors.initials: PF
authors.lastname: Pilch
mesh_terms: D003432:Cross-Linking Reagents / Q000494:pharmacology; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008861:Microsomes / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011972:Receptor, Insulin / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology
chemical_list: D003432:Cross-Linking Reagents; D007328:Insulin; D046911:Macromolecular Substances; D013388:Succinimides; D011972:Receptor, Insulin; C019358:disuccinimidyl suberate