Loop mutations affect ferritin solubility causing non-native aggregation of subunits or precipitation of fully assembled polymers.

Abstract

As a consequence of elevated expression rates, the intracellular aggregation of polypeptide chains is commonly observed in E. coli. Although wild-type human ferritin, a polymeric iron storage protein, accumulates in the soluble form at high level in the bacterial cytoplasmic fraction, some amino acid substitutions in an exposed loop direct the synthesis of a highly insoluble product. We found that two mechanisms can lead to the aggregation of ferritin. While some mutations prevent ferritin polymerisation, others cause the precipitation of molecules in the assembled state.