Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery
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 o...
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Elsevier
2019-11-01
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| Series: | Current Research in Structural Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665928X19300029 |
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doaj-3a4bafe2973a426e8039983c811a2c882020-11-25T03:41:47ZengElsevierCurrent Research in Structural Biology2665-928X2019-11-0111320Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machineryIstvan Botos0George T. Lountos1Weimin Wu2Scott Cherry3Rodolfo Ghirlando4Arsen M. Kudzhaev5Tatyana V. Rotanova6Natalia de Val7Joseph E. Tropea8Alla Gustchina9Alexander Wlodawer10Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USAMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USACenter for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USAMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USALaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USAShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, RussiaCenter for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Electron Microscopy Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USAMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USAMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USAMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2665928X19300029AAA+ proteinsATPase moduleLon proteaseCryo-EM |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery Current Research in Structural Biology AAA+ proteins ATPase module Lon protease Cryo-EM |
| author_facet |
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 |
| author_sort |
Istvan Botos |
| title |
Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery |
| title_short |
Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery |
| title_full |
Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery |
| title_fullStr |
Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery |
| title_full_unstemmed |
Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery |
| title_sort |
cryo-em structure of substrate-free e. coli lon protease provides insights into the dynamics of lon machinery |
| publisher |
Elsevier |
| series |
Current Research in Structural Biology |
| issn |
2665-928X |
| publishDate |
2019-11-01 |
| description |
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. |
| topic |
AAA+ proteins ATPase module Lon protease Cryo-EM |
| url |
http://www.sciencedirect.com/science/article/pii/S2665928X19300029 |
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