Conversion of a Chaperonin GroEL-Independent Protein into an Obligate Substrate [Protein Structure and Folding]

October 6th, 2014 by Ishimoto, T., Fujiwara, K., Niwa, T., Taguchi, H.

Chaperones assist protein folding by preventing unproductive protein aggregation in the cell. In Escherichia coli, chaperonin GroEL/GroES (GroE) is the only indispensable chaperone and is absolutely required for the de novo folding of at least ~60 proteins. We previously found that several orthologs of the obligate GroE substrates in Ureaplasma urealyticum, which lacks the groE gene in the genome, are E. coli GroE-independent folders, despite their significant sequence identities. Here, we investigated the key features that define the GroE-dependency. Chimera or random mutagenesis analyses revealed that independent multiple point mutations, and even single mutations, were sufficient to confer GroE-dependence on the Ureaplasma MetK. Strikingly, the GroE-dependency was well correlated with the propensity to form protein aggregates during folding. The results reveal the delicate balance between GroE-dependence and independence. The function of GroE to buffering the aggregation-prone mutations plays a role in maintaining higher genetic diversity of proteins.