AimB Is a Small Protein Regulator of Cell Size and MreB Assembly.

TitleAimB Is a Small Protein Regulator of Cell Size and MreB Assembly.
Publication TypeJournal Article
Year of Publication2020
AuthorsWerner, JN, Shi, H, Hsin, J, Huang, KCasey, Gitai, Z, Klein, EA
JournalBiophys J
Date Published2020 Aug 04
KeywordsActins, Bacterial Proteins, Caulobacter crescentus, Cell Size, Cytoskeleton, Escherichia coli Proteins

<p>The MreB actin-like cytoskeleton assembles into dynamic polymers that coordinate cell shape in many bacteria. In contrast to most other cytoskeleton systems, few MreB-interacting proteins have been well characterized. Here, we identify a small protein from Caulobacter crescentus, an assembly inhibitor of MreB (AimB). AimB overexpression mimics inhibition of MreB polymerization, leading to increased cell width and MreB delocalization. Furthermore, aimB appears to be essential, and its depletion results in decreased cell width and increased resistance to A22, a small-molecule inhibitor of MreB assembly. Molecular dynamics simulations suggest that AimB binds MreB at its monomer-monomer protofilament interaction cleft and that this interaction is favored for C. crescentus MreB over Escherichia coli MreB because of a closer match in the degree of opening with AimB size, suggesting coevolution of AimB with MreB conformational dynamics in C. crescentus. We support this model through functional analysis of point mutants in both AimB and MreB, photo-cross-linking studies with site-specific unnatural amino acids, and species-specific activity of AimB. Together, our findings are consistent with AimB promoting MreB dynamics by inhibiting monomer-monomer assembly interactions, representing a new mechanism for regulating actin-like polymers and the first identification of a non-toxin MreB assembly inhibitor. Because AimB has only 104 amino acids and small proteins are often poorly characterized, our work suggests the possibility of more bacterial cytoskeletal regulators to be found in this class. Thus, like FtsZ and eukaryotic actin, MreB may have a rich repertoire of regulators to tune its precise assembly and dynamics.</p>

Alternate JournalBiophys J
PubMed ID32416080
PubMed Central IDPMC7399478
Grant ListF32 GM100677 / GM / NIGMS NIH HHS / United States
P50 GM107615 / GM / NIGMS NIH HHS / United States
R01 GM107384 / GM / NIGMS NIH HHS / United States