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


Change log
Abstract

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.

Description
Keywords
AAA+, Lon, cell cycle, coiled-coil, protease, unfolding, Cryoelectron Microscopy, Protease La, Proteolysis, Thermus thermophilus
Journal Title
FEBS Lett
Conference Name
Journal ISSN
0014-5793
1873-3468
Volume Title
Publisher
Wiley
Sponsorship
Medical Research Council (U105184326)
Wellcome Trust (202754/Z/16/Z)