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The catalytic dwell in ATPases is not crucial for movement against applied torque

Nature Chemistry volume 12, pages 1187–1192 (2020)Cite this article

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Abstract

The ATPase-catalysed conversion of ATP to ADP is a fundamental process in biology. During the hydrolysis of ATP, the α3β3 domain undergoes conformational changes while the central stalk (γ/D) rotates unidirectionally. Experimental studies have suggested that different catalytic mechanisms operate depending on the type of ATPase, but the structural and energetic basis of these mechanisms remains unclear. In particular, it is not clear how the positions of the catalytic dwells influence the energy transduction. Here we show that the observed dwell positions, unidirectional rotation and movement against the applied torque are reflections of the free-energy surface of the systems. Instructively, we determine that the dwell positions do not substantially affect the stopping torque. Our results suggest that the three resting states and the pathways that connect them should not be treated equally. The current work demonstrates how the free-energy landscape determines the behaviour of different types of ATPases.

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Fig. 1: Coupled free-energy maps of the α3β3 subunit conformational change and the γ/D stalk rotation.
Fig. 2: Conformational/catalytic free-energy surfaces.
Fig. 3: The PMF calculated from the conformational/catalytic surface.

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Data availability

The cryo-EM structures used in this work are available from the Protein Data Bank under PDB IDs 6RD9, 6RDC and 6REP for mF1; 6FKF, 6FKI and 6FKH for cF1; and 6QUM, 6R0W and 6R0Y for V1. The CG structure and input codes for CG relaxation and MCPT calculation are available freely online: https://doi.org/10.6084/m9.figshare.12768413.v2

Code availability

The MOLARIS-XG package is available upon request from the University of Southern California.

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Acknowledgements

This work was supported by the National Science Foundation grant MCB 1707167 and the National Institute of Health grant R01-AI055926. We thank the University of Southern California High Performance Computing and Communication Center (HPCC), as well as the Extreme Science and Engineering Discovery Environment’s (XSEDE) Comet facility at the San Diego Supercomputing Center, for computational resources.

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Authors and Affiliations

  1. Department of Chemistry, University of Southern California, Los Angeles, CA, USA

    Chen Bai, Mojgan Asadi & Arieh Warshel

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  1. Chen Bai
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Contributions

C.B. and A.W. conceived and designed the project. C.B. designed, executed and analysed all experiments with guidance from A.W. M.A. executed and analysed part of the experiments with assistance and guidance from C.B. and A.W. C.B. wrote the input and analysis codes for all experiments. C.B. and A.W. wrote the manuscript with input from all authors.

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Correspondence to Arieh Warshel.

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Supplementary Figs. 1 and 2 and discussion.

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Bai, C., Asadi, M. & Warshel, A. The catalytic dwell in ATPases is not crucial for movement against applied torque. Nat. Chem. 12, 1187–1192 (2020). https://doi.org/10.1038/s41557-020-0549-6

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