Cryo-EM structure of the full-length Lon protease from Thermus thermophilus

In bacteria, Lon is a large hexameric ATP-dependent protease that targets misfolded and also folded substrates, some of which are involved in cell division and survival of cellular stress. The N-terminal domain of Lon facilitates substrate recognition, but how the domains confer such activity has remained unclear. Here, we report the full-length structure of Lon protease from Thermus thermophilus at 3.9 angstrom resolution in a substrate-engaged state. The six N-terminal domains are arranged in three pairs, stabilized by coiled-coil segments and forming an additional channel for substrate sensing and entry into the AAA+ ring. Sequence conservation analysis and proteolysis assays confirm that this architecture is required for the degradation of both folded and unfolded substrates in bacteria.

Automated summary

Lon protease in bacteria is an ATP-dependent protease targeting misfolded and folded substrates, with the N-terminal domains facilitating substrate recognition and degradation. The full-length structure of Lon protease from Thermus thermophilus reveals a unique architecture essential for substrate sensing and entry into the AAA+ ring, confirming its role in degrading substrates in bacteria.