Structures of the nucleoid occlusion protein SlmA bound to DNA and the C-terminal domain of the cytoskeletal protein FtsZ.
Cell division in most prokaryotes is mediated by FtsZ, which polymerizes to create the cytokinetic Z ring. Multiple FtsZ-binding proteins regulate FtsZ polymerization to ensure the proper spatiotemporal formation of the Z ring at the division site. The DNA-binding protein SlmA binds to FtsZ and prevents Z-ring formation through the nucleoid in a process called "nucleoid occlusion" (NO). As do most FtsZ-accessory proteins, SlmA interacts with the conserved C-terminal domain (CTD) that is connected to the FtsZ core by a long, flexible linker. However, SlmA is distinct from other regulatory factors in that it must be DNA-bound to interact with the FtsZ CTD. Few structures of FtsZ regulator-CTD complexes are available, but all reveal the CTD bound as a helix. To deduce the molecular basis for the unique SlmA-DNA-FtsZ CTD regulatory interaction and provide insight into FtsZ-regulator protein complex formation, we determined structures of Escherichia coli, Vibrio cholera, and Klebsiella pneumonia SlmA-DNA-FtsZ CTD ternary complexes. Strikingly, the FtsZ CTD does not interact with SlmA as a helix but binds as an extended conformation in a narrow, surface-exposed pocket formed only in the DNA-bound state of SlmA and located at the junction between the DNA-binding and C-terminal dimer domains. Binding studies are consistent with the structure and underscore key interactions in complex formation. Combined, these data reveal the molecular basis for the SlmA-DNA-FtsZ interaction with implications for SlmA's NO function and underscore the ability of the FtsZ CTD to adopt a wide range of conformations, explaining its ability to bind diverse regulatory proteins.
Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710 maria.schumacher@duke.edu.
Maria A
MA
Schumacher
Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710.
Wenjie
W
Zeng
D001426:Bacterial Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D020090:Chromosome Segregation; D002876:Chromosomes, Bacterial / Q000737:chemistry / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D004269:DNA, Bacterial / Q000737:chemistry* / Q000648:ultrastructure*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000648:ultrastructure; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D000072417:Protein Domains; D021122:Protein Subunits
D001426:Bacterial Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C071525:FtsZ protein, Bacteria; D021122:Protein Subunits; C502032:SlmA protein, E coli
FtsZ; SlmA; cell division; nucleoid occlusion; protein–protein interaction