Distinct Quaternary Structures of Lon Protease Control Substrate Degradation

The Lon protease controls cell division in response to stress and is the major protease that degrades misfolded and damaged proteins. Previous studies indicated that Lon is a ring-shaped homo-hexamer. using biophysical techniques we now demonstrate that E. coli Lon also exists as larger oligomers at physiological protein concentrations. The structure of these large complexes, reconstructed by electron microscopy, reveals that Lon assembles into a dodecamer in which the protease cores are on the distal ends and the two hexamers are linked by a matrix formed by the N domains. Importantly, the Lon hexamer is ∼10-fold faster ATPase and is ∼20-fold more active in degrading some classes of substrates than is the dodecamer. This difference in degradation rate is not observed with small degron tagged substrates. We propose a model in which the Lon dodecamer uses a gating mechanism to exclude some classes of proteins allowing the enzyme's substrate profile to be altered by its assembly state.View Large Image | View Hi-Res Image | Download PowerPoint Slide