Computational assessment of bacterial protein structures indicates a selection against aggregation

Abstract

The aggregation of proteins compromises cell fitness, either because it titrates functional proteins into non-productive inclusions or because it results in the formation of toxic assemblies. Accordingly, computational proteome-wide analyses suggest that prevention of aggregation upon misfolding plays a key role in sequence evolution. Most proteins spend their lifetimes in a folded state; therefore, it is conceivable that, in addition to sequences, protein structures would have also evolved to minimize the risk of aggregation in their natural environments. By exploiting the AGGRESCAN3D structure-based approach to predict the aggregation propensity of >600 Escherichia coli proteins, we show that the structural aggregation propensity of globular proteins is connected with their abundance, length, essentiality, subcellular location and quaternary structure. These data suggest that the avoidance of protein aggregation has contributed to shape the structural properties of proteins in bacterial cells.