A conserved cell division protein directly regulates FtsZ dynamics in filamentous and unicellular actinobacteria

Abstract

Bacterial cell division is driven by the polymerization of the GTPase FtsZ into a contractile structure, the so-called Z-ring. This essential process involves proteins that modulate FtsZ dynamics and hence the overall Z-ring architecture. Actinobacteria, like Streptomyces and Mycobacterium lack known key FtsZ-regulators. Here we report the identification of SepH, a conserved actinobacterial protein that directly regulates FtsZ dynamics. We show that SepH is crucially involved in cell division in Streptomyces and that it binds FtsZ via a conserved helix-turn-helix motif, stimulating the assembly of FtsZ protofilaments. Comparative in vitro studies using the SepH homolog from Mycobacterium further reveal that SepH can also bundle FtsZ protofilaments, indicating an additional Z-ring stabilizing function in vivo. We propose that SepH plays a crucial role at the onset of cytokinesis in actinobacteria by promoting the rapid assembly of FtsZ filaments into division-competent Z-rings that can go on to mediate septum synthesis.

Hyphal compartmentalization and sporulation in Streptomyces require the conserved cell division protein SepX

“…The complete data set is included in the Source Data. (c) Schematic showing the proposed SepX interaction network, including DynB and several known S. venezuelae divisome components 11,12 .…”

“…The Streptomyces life cycle is characterized by two distinct FtsZ-dependent modes of cell division that lead to the separation of growing hyphal filaments into multigenomic compartments and to the formation and release of unigenomic spores. While some recent progress has been made towards the understanding of the components involved in sporulation-specific sporulation 6,8,11,12 , little has been known about the determinants for FtsZ-mediated cross-wall formation. Here we describe the previously unknown cell division protein SepX, which is crucial for cross-wall formation and sporulation in Streptomyces .…”

“…work had demonstrated that DynB is involved in Z-ring sta during sporulation-specific cell division and associates divisome by binding to SsgB and SepF2, which in turn directly (SsgB) or indirectly (SepF2) connected with the Thus, our protein-protein interaction studies place SepX in a n interactions involving key divisome components involved in positioning, anchoring and stability (Figure 5c). 11,12 .…”

“…Moreover, additional factors have been identified that associate with the divisome and/or contribute to the efficient assembly and stability of Z-rings. These proteins include the actinobacterial-specific protein SsgB, which has been reported to mark future sporulation-septation sites 8 , SepF, which functions as a membrane anchor for FtsZ [9][10][11] , SepH, which stimulates FtsZ filament assembly 12 , the two dynamin-like proteins DynA and DynB, which stabilize FtsZ-rings during sporulation, and two SepF-like proteins of unknown function 11 . Previous genetic studies have shown that none of the conserved and species-specific cell division proteins are essential for growth and viability in Streptomyces 6,7 .…”

Structural, Metabolic and Evolutionary Comparison of Bacterial Endospore and Exospore Formation

“…Instead, Streptomyces utilizes SepF homologs to anchor Z rings to the membrane during cell division in sporulation ( Schlimpert et al, 2017 ). SepH, an Actinobacterial specific protein, is also integral for establishing the formation of Z rings ( Ramos-Léon et al, 2020 ). However, it is unclear how SepH is initially localized and whether it interacts with other proteins for positioning of the Z rings.…”