Product-stabilized filamentation by human glutamine synthetase allosterically tunes activity

Metabolic enzymes need to quickly adapt to fluctuating nutrient levels in order to maintain cell viability. One way to regulate enzyme activity is by assembling them into filamentous structures. In this study, we discovered a new filament interface in human glutamine synthetase (GS) that forms a composite binding site for the enzyme's reaction product, glutamine. We confirmed the presence of glutamine at the filament interface using time-resolved cryoEM along the reaction coordinate of GS and subsequent glutamine-only containing cryoEM datasets.