Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery

• Main Authors: Istvan Botos, George T. Lountos, Weimin Wu, Scott Cherry, Rodolfo Ghirlando, Arsen M. Kudzhaev, Tatyana V. Rotanova, Natalia de Val, Joseph E. Tropea, Alla Gustchina, Alexander Wlodawer
• Format: Article
• Language: English
• Published: Elsevier 2019-11-01
• Series: Current Research in Structural Biology
• Subjects: AAA+ proteins; ATPase module; Lon protease; Cryo-EM
• Online Access: http://www.sciencedirect.com/science/article/pii/S2665928X19300029
• ISSN: 2665-928X

Energy-dependent Lon proteases play a key role in cellular regulation by degrading short-lived regulatory proteins and misfolded proteins in the cell. The structure of the catalytically inactive S679A mutant of Escherichia coli LonA protease (EcLon) has been determined by cryo-EM at the resolution of 3.5 Å. EcLonA without a bound substrate adopts a hexameric open-spiral quaternary structure that might represent the resting state of the enzyme. Upon interaction with substrate the open-spiral hexamer undergoes a major conformational change resulting in a compact, closed-circle hexamer as in the recent structure of a complex of Yersinia pestis LonA with a protein substrate. This major change is accomplished by the rigid-body rearrangement of the individual domains within the protomers of the complex around the hinge points in the interdomain linkers. Comparison of substrate-free and substrate-bound Lon structures allows to mark the location of putative pivotal points involved in such conformational changes.