Mutation Ala2 → Ser Destabilizes Intersubunit Interactions in the Molecular Chaperone GroEL

Abstract

The mutations Ala2 → Ser in the molecular chaperone GroEL increases positive co-operativity in ATP hydrolysis, as reflected by a change in the Hill coefficient from 2·36(±0·23) for wild-type to 3·19(±0·17) for the mutant. This amino acid replacement destabilizes the oligomeric structure of GroEL. It is shown that adenine nucleotides also have a specific destabilizing effect which is more pronounced in the case of the Ala2 → Ser mutant. Addition of GroES or the non-folded protein ligand rhodanese blocks the destabilizing effect of adenine nucleotides for both wild-type and mutant. The results are interpreted using the Monod-Wyman-Changeux (MWC) model for co-operatively.