EFFECTS OF THE INTERRING COMMUNICATION IN GROEL STRUCTURAL AND FUNCTIONAL ASYMMETRY

The chaperonin GroEL consists of a double-ring structure that assists protein folding in the presence of GroES and ATP, Recent studies sugge st that the 7-mer ring is the functional unit where protein folding ta kes place, Nevertheless, both GroEL rings are required to complete the reaction cycle through signals transmitted between the two rings, Ele ctron microscopy, image processing, and biochemical analysis of GroEL, a single-ring mutant (SR1) and a inter-ring communication affected mu tant (A126V), in the presence of ATP and adenylyl imidodiphosphate, ha ve allowed the identification of a conformational change in the apical domains that is strictly dependent on the communication be tween the two GroEL rings, It is deduced from these results that the binding of nucleotide to both GroEL rings generates, as a consequence of the inte r-ring communication, a functionally and structurally asymmetric parti cle. This asymmetric particle has a ring with a small conformational c hange in its apical domains and high affinity toward unfolded substrat e and GroES, and the other ring has a larger conformational change in its apical domains and lower affinity toward substrate and GroES.