Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 9, Pages 3585-3590Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1317061111
Keywords
bacterial cytoskeleton; polymer mechanics; actin superfamily; filament assembly; cell shape control
Categories
Funding
- Stanford Graduate Fellowship
- National Institutes of Health Ruth L. Kirschstein National Research Service Award [1F32GM100677]
- Stanford School of Medicine Dean's Postdoctoral Fellowship
- National Science Foundation CAREER Award [MCB-1149328]
- National Institutes of Health (NIH) Director's New Innovator Award [DP2OD006466]
- Simbios NIH Center for Biomedical Computation [U54 GM072970]
- National Science Foundation [OCI-1053575]
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The assembly of protein filaments drives many cellular processes, from nucleoid segregation, growth, and division in single cells to muscle contraction in animals. In eukaryotes, shape and motility are regulated through cycles of polymerization and depolymerization of actin cytoskeletal networks. In bacteria, the actin homolog MreB forms filaments that coordinate the cell-wall synthesis machinery to regulate rod-shaped growth and contribute to cellular stiffness through unknown mechanisms. Like actin, MreB is an ATPase and requires ATP to polymerize, and polymerization promotes nucleotide hydrolysis. However, it is unclear whether other similarities exist between MreB and actin because the two proteins share low sequence identity and have distinct cellular roles. Here, we use all-atom molecular dynamics simulations to reveal surprising parallels between MreB and actin structural dynamics. We observe that MreB exhibits actin-like polymerization-dependent structural changes, wherein polymerization induces flattening of MreB subunits, which restructures the nucleotide-binding pocket to favor hydrolysis. MreB filaments exhibited nucleotide-dependent inter-subunit bending, with hydrolyzed polymers favoring a straighter conformation. We use steered simulations to demonstrate a coupling between intersubunit bending and the degree of flattening of each subunit, suggesting cooperative bending along a filament. Taken together, our results provide molecular-scale insight into the diversity of structural states of MreB and the relationships among polymerization, hydrolysis, and filament properties, which may be applicable to other members of the broad actin family.
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