Featured Article - October 2009
Short description: Streptomyces' unique mechanism for cell division comes under the spotlight and reveals the importance of the protein SsgB.
Cell division has been extensively studied, but many mysteries still remain. Studies using the unicellular bacterium Escherichia coli hinted at a mechanism that revolves around the prokaryotic cell-division protein FtsZ, which was found to be structurally similar to the eukaryotic protein tubulin.
Unfortunately, it wasn't that simple. When researchers examined the bacterium Streptomyces, an important source of antibiotics and anti-cancer agents, they found that, while it requires FtsZ for cell division, it is not essential for growth as in other organisms. Also, the proteins required for septum localization were missing. Unlike E. coli, Streptomyces does not divide by simply splitting into two, instead it multiplies by sporulation. In the process, they produce up to one hundred septa simultaneously.
To achieve this, Streptomyces has several unique protein families, including SsgA-like proteins. These small proteins control sporulation by controlling the position of the septum and the thickness of the spore wall, as well as regulating spore separation. However, little was known about this family of proteins until an international team involving PSI JCSG, PSI MCSG, Leiden University in the Netherlands and other groups published a paper in the Journal of Biological Chemistry 1 .
They looked at SsgB, the only member of the SsgA-like family conserved in all sporulating actinomycetes, and asked whether an SsgB from one species can work in another. Using a previously established assay with the bacterium Streptomyces coelicolor they tested several SsgB orthologs and found that sporulation-specific cell division was possible even with distantly related orthologs. They also noted that the number of septa and resultant spores depended on the ssgB ortholog used rather than being dictated by other S. coelicolor genes.
The crystal structure of the SsgB ortholog from Thermobifida fusca shows that it is a single-domain protein with eight β-strands and three α-helices arranged in an α+β fold. It contains two tandem repeats of a four-stranded β-sheet and an α-helix motif. Comparison of the structures with those in the PDB found that it was most similar to the mitochondrial RNA-binding protein 2 from Trypanosoma bruciei, despite little sequence similarity. However, detailed analysis suggests that SsgB does not have the concave surface needed for nucleotide binding neither does it have the necessary surface charge.
These experiments show that SsgB controls septum-site localization and has a structure that is different from all previously known cell-division proteins. It is likely that SsgB makes hydrophobic contacts involving a conserved Trp54 on its surface with protein partners, which ultimately form a complex that controls sporulation.
Xu et al. Structural and functional characterization of SsgB, a conserved activator of developmental cell division in morphologically complex actinomycetes.
J. Biol. Chem. 284, 25268-25279 (2009). doi:10.1074/jbc.M109.018564