A MODEL FOR THE QUATERNARY STRUCTURE OF HUMAN PLACENTAL INSULIN-RECEPTOR DEDUCED FROM ELECTRON-MICROSCOPY

Electrophoretically pure and functionally intact human placental insulin receptor was studied by electron microscopy with negative-staining techniques. The quaternary structure of the detergent-solubilized receptor was determined. The receptor had the shape of a letter T almost-equal-to 24 nm in height and 18 nm in width with a thickness of the stem and the crossbar of 3-4 nm. No consistent change in ultrastructure of the receptor could be detected after the addition of insulin alone or insulin and Mn2+/Mg2+/ATp. After partial reduction of the alpha-2-beta-2 heterotetrameric receptor into alpha-beta heterodimers, the electron micrographs showed a clear reduction in average size of the molecule with disappearance of the T profiles characteristic of the alpha-2-beta-2 heterotetramers. By incubation of the heterodimers in a phosphorylation medium containing insulin, a reassociation of molecules with molecular weights of the alpha-2-beta-2 heterotetramer took place judged from SDS/PAGE. Electron microscopy showed that the molecule formed larger aggregates, and only a few solitary T-shaped copies were seen.