RESUMEN
Chaperonins mediate protein folding in an ATP-dependent manner. ATP binding and hydrolysis by chaperonins are subject to both homotropic and heterotropic allosteric regulation. In the case of GroEL and CCT, homotropic regulation by ATP is manifested in nested cooperativity, which involves positive intra-ring cooperativity and negative inter-ring cooperativity in ATP binding. Both types of cooperativity are modulated by various heterotropic allosteric effectors, which include nonfolded proteins, ADP, Mg2+, monovalent ions such as K+, and cochaperonins in the case of type I chaperonins such as GroEL. Here, the allosteric properties of chaperonins are reviewed and new results of ours are presented with regard to allosteric effects of ADP. The role of allostery in the reaction cycle and folding function of chaperonins is discussed.
Asunto(s)
Regulación Alostérica/fisiología , Chaperoninas/efectos de los fármacos , Animales , Humanos , Cinética , Ligandos , Modelos Químicos , Proteínas/metabolismo , Proteínas/farmacologíaRESUMEN
Initial rates of ATP hydrolysis by the chaperonin containing TCP-1 (CCT) from bovine testis were measured as a function of ATP concentration. Two allosteric transitions are observed: one at relatively low concentrations of ATP (<100 microM) and the second at higher concentrations of ATP. The data suggest that CCT has positive intra-ring cooperativity and negative inter-ring cooperativity in ATP hydrolysis, with respect to ATP, as previously observed in the case of GroEL. It is shown that the relatively weak positive intra-ring cooperativity found in the case of CCT may be due to heterogeneity in its subunit composition. Our results suggest that nested allosteric behavior may be common to chaperone double-ring systems.