Greater than the sum of parts: Mechanisms of metabolic regulation by enzyme filaments.

Recent work in structural biology is shedding light on how many of the enzymes of intermediary metabolism are self- and co-assembling into large, filamentous polymers or agglomerates to organize and regulate the complex and essential biochemical pathways in cells. Filament assembly provides an additional layer of regulation by modulating the intrinsic allostery of the enzyme protomers which tunes activity in response to a variety of environmental cues. Enzyme filaments dynamically assemble and disassemble in response to changes in metabolite levels and environmental cues, shifting metabolic flux on a more rapid timescale than transcriptional or translational reprogramming. Here we present recent examples of high-resolution structures of filaments from proteins in intermediary metabolism and we discuss how filament assembly modulates the activities of these and other proteins.