Multiple conserved states characterize the twist landscape of the bacterial actin homolog MreB

Benjamin D Knapp; Michael D Ward; Gregory R Bowman; Handuo Shi; Kerwyn Casey Huang

doi:10.1016/j.csbj.2022.10.008

Multiple conserved states characterize the twist landscape of the bacterial actin homolog MreB

Comput Struct Biotechnol J. 2022 Oct 7:20:5838-5846. doi: 10.1016/j.csbj.2022.10.008. eCollection 2022.

Authors

Benjamin D Knapp¹, Michael D Ward^{2

3}, Gregory R Bowman^{2

3}, Handuo Shi^{4

5}, Kerwyn Casey Huang^{1

4

5

6}

Affiliations

¹ Biophysics Program, Stanford University, Stanford, CA 94305, USA.
² Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63130, USA.
³ Center for the Science and Engineering of Living Systems, Washington University in St. Louis, St. Louis, MO 63130, USA.
⁴ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁵ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
⁶ Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.

Abstract

Filament formation by cytoskeletal proteins is critical to their involvement in myriad cellular processes. The bacterial actin homolog MreB, which is essential for cell-shape determination in many rod-shaped bacteria, has served as a model system for studying the mechanics of cytoskeletal filaments. Previous molecular dynamics (MD) simulations revealed that the twist of MreB double protofilaments is dependent on the bound nucleotide, as well as binding to the membrane or the accessory protein RodZ, and MreB mutations that modulate twist also affect MreB spatial organization and cell shape. Here, we show that MreB double protofilaments can adopt multiple twist states during microsecond-scale MD simulations. A deep learning algorithm trained only on high- and low-twist states robustly identified all twist conformations across most perturbations of ATP-bound MreB, suggesting the existence of a conserved set of states whose occupancy is affected by each perturbation to MreB. Simulations replacing ATP with ADP indicated that twist states were generally stable after hydrolysis. These findings suggest a rich twist landscape that could provide the capacity to tune MreB activity and therefore its effects on cell shape.

Keywords: Actin homologs; Bacterial cytoskeleton; Chiral twist; Deep learning; DiffNets; Molecular dynamics.

Grants and funding

R01 GM116961/GM/NIGMS NIH HHS/United States