title: Dimer dynamics and filament organization of the bacterial cell division protein FtsA.
abstract: FtsA is a bacterial actin homolog and one of the core proteins involved in cell division. While previous studies have demonstrated the capability of FtsA to polymerize, little is known about its polymerization state in vivo or if polymerization is necessary for FtsA function. Given that one function of FtsA is to tether FtsZ filaments to the membrane, in vivo polymerization of FtsA imposes geometric constraints and requires a specific polymer curvature direction. Here, we report a series of molecular dynamics simulations probing the structural dynamics of FtsA as a dimer and as a tetrameric single filament. We found that the FtsA polymer exhibits a preferred bending direction that would allow for its placement parallel with FtsZ polymers underneath the cytoplasmic membrane. We also identified key interfacial amino acids that mediate FtsA-FtsA interaction and propose that some amino acids play more critical roles than others. We performed in silico mutagenesis on FtsA and demonstrated that, while a moderate mutation at the polymerization interface does not significantly affect polymer properties such as bending direction and association strength, more drastic mutations change both features and could lead to non-functional FtsA.
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jen
authors.initials: J
authors.lastname: Hsin
authors.forename: Rui
authors.initials: R
authors.lastname: Fu
authors.forename: Kerwyn Casey
authors.initials: KC
authors.lastname: Huang
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002455:Cell Division; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C065103:FtsA protein, Bacteria; C071525:FtsZ protein, Bacteria
keywords: actin family; bacterial cytoskeleton; cell division; molecular dynamics; polymer mechanics