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Recently, we reported the first data on the relationship between GroEL-assisted protein folding rates and allostery in GroEL (Yifrach and Horovitz, 2000). Using different cooperativity mutants of GroEL, a linear relationship was found between the folding rate of mouse dihydrofolate reductase (under conditions where its folding is GroEL-dependent but GroES-independent) and the rate of the T®R transition. This relationship is also reflected in the values of the Hill coefficients for these transitions. We also found linear relationships between the folding rate of mouse dihydrofolate reductase and the extent of inter-ring negative cooperativity. Little is known, however, about the relationship between rates of folding of GroES-dependent substrates and allostery in the presence of GroES. One reason for this is that there is little data on cooperativity in the GroES-bound ring of GroEL. Previously, we showed that GroES binding to one ring of GroEL reduces cooperativity in the other distal ring of GroEL (Inbar et al., 1997). We are now trying to determine the extent of cooperativity in the GroES-bound ring and its impact on the folding of GroES-dependent substrates. In addition, we have also been analysing the importance of allostery in GroEL in vivo by generating E. coli strains which express only plasmid-derived GroEL (wild-type or different mutants which are defective in their allosteric properties) and characterizing their phenotypes (Fridmann et al., 2000).