Structure of the thyrotropin receptor and thyroid adenylate cyclase system as determined by target analysis.
Bovine thyroid plasma membranes were irradiated with high-energy electrons. Analysis of the target size of the thyrotropin (TSH) receptor revealed a complex pattern composed of a TSH binding component of 71 000 daltons and a large component (several hundred thousand daltons) that masked some of the binding. Both components were also observed when binding was assayed in the presence of 50 mM NaCl. Membranes preincubated with Mg2+ and 10 microM guanosine 5'-(beta,gamma-imidotriphosphate) [Gpp(NH)p], a persistent activator of adenylate cyclase, also showed the presence of these same components. Although the receptor for TSH has been reported to have some similarities to the receptor for cholera toxin, target analysis of [125I]iodocholera toxin binding was consistent with a single small component about the size of a ganglioside. Measurement of the target size of ground-state, i.e., not preactivated, adenylate cyclase was also carried out. The basal (Mn2+) adenylate cyclase yielded a Mr of 85 000, the smallest unit capable of producing cAMP. The Gpp(NH)p-responsive adenylate cyclase has a Mr of 150 000, which may reflect the contribution of the guanine nucleotide regulatory component to the mass of the active enzyme. A similar size was previously measured for the Gpp(NH)p-preactivated, detergent-solubilized thyroid enzyme [Asbury, R.F., Cook, G.H., & Wolff, J. (1978) J. Biol. Chem. 253, 5286-5292]. Radiation inactivation of the NaF-responsive enzyme indicated two or more components to this activity, the smaller of which (140 000 daltons) was similar in size to the ground-state Gpp(NH)p-responsive enzyme and the larger of which was greater than 10(6) daltons.(ABSTRACT TRUNCATED AT 250 WORDS)
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D011989:Receptors, Thyrotropin; D012965:Sodium Chloride / Q000494:pharmacology; D013961:Thyroid Gland / Q000378:metabolism* / Q000528:radiation effects; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology
D011956:Receptors, Cell Surface; D011989:Receptors, Thyrotropin; D006165:Guanylyl Imidodiphosphate; D012965:Sodium Chloride; D013972:Thyrotropin; D002772:Cholera Toxin; D000262:Adenylyl Cyclases; D008274:Magnesium