Papachristos, K, Muench, SP orcid.org/0000-0001-6869-4414 and Paci, E orcid.org/0000-0002-4891-2768 (2016) Characterization of the flexibility of the peripheral stalk of prokaryotic rotary A-ATPases by atomistic simulations. Proteins, 84 (9). pp. 1203-1212. ISSN 0887-3585
Abstract
Rotary ATPases are involved in numerous physiological processes, with the three distinct types (F/A/V-ATPases) sharing functional properties and structural features. The basic mechanism involves the counter rotation of two motors, a soluble ATP hydrolyzing/synthesizing domain and a membrane-embedded ion pump connected through a central rotor axle and a stator complex. Within the A/V-ATPase family conformational flexibility of the EG stators has been shown to accommodates catalytic cycling and is considered to be important to function. For the A-ATPase three EG structures have been reported, thought to represent conformational states of the stator during different stages of rotary catalysis. Here we use long, detailed atomistic simulations to show that those structures are conformers explored through thermal fluctuations, but do not represent highly populated states of the EG stator in solution. We show that the coiled coil tail domain has a high persistence length (∼100nm), but retains the ability to adapt to different conformational states through the presence of two hinge regions. Moreover, the stator network of the related V-ATPase has been suggested to adapt to subunit interactions in the collar region and not the nucleotide occupancy of the catalytic domain. The MD simulations reported here, reinforce this observation showing that the EG stators have enough plasticity to adapt to significantly different structural re-arrangements and accommodate structural changes in the catalytic domain whilst resisting the large torque generated by catalytic cycling. These results are important to understand the role the stators play in the rotary-ATPase mechanism.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | molecular dynamics; protein mechanics; rotary ATPases |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 16 Jun 2016 11:06 |
Last Modified: | 23 Jun 2023 22:07 |
Published Version: | http://dx.doi.org/10.1002/prot.25066 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/prot.25066 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:100932 |