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

Francesca Coscia, Jan Löwe

OAI: oai:www.repository.cam.ac.uk:1810/329569 • DOI: 10.17863/CAM.77017

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 Å 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.

AAA+ Lon Cell Cycle Coiled-coil Protease unfolding Cryoelectron Microscopy Protease La Proteolysis Thermus thermophilus