Insulin-induced dissociation of its receptor into subunits: possible molecular concomitant of negative cooperativity.
The detergent-solubilized avian insulin receptor retains negative cooperativity and other binding properties of the membrane bound form. On gel filtration the receptor elutes as a single peak with a Stokes radius of 72 A. Preincubation of the receptor with low levels of insulin leads to the formation of a second, smaller form with a Stokes radius of 40 A. The percent of receptor in this second peak is proportional to the insulin concentration and correlates well with the insulin-induced increase in dissociation rate (negative cooperativity). Both the isolated high molecular weight and the isolated low-molecular-weight forms of the receptor re-equilibrate in the presence of insulin and, upon refiltration of either isolated peak, both forms of the receptor are obtained. These results are compatible with a model of the insulin receptor in which a tetrameric form can dissociate to a monomeric form as a concomitant of negative cooperativity.
Ginsberg
B H
BH
Diabetes Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014, USA.
Kahn
C R
CR
Roth
J
J
De Meyts
P
P
D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001717:Birds; D002850:Chromatography, Gel; D007328:Insulin / Q000494:pharmacology*; D021122:Protein Subunits / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D011972:Receptor, Insulin / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*
D007328:Insulin; D021122:Protein Subunits; D011972:Receptor, Insulin