Intrinsically disordered protein regions are required for cell wall homeostasis in Bacillus subtilis

Intrinsically disordered protein regions (IDRs) have been implicated in diverse nuclear and cytoplasmic functions in eukaryotes, but their roles in bacteria are less clear. Here, we report that extracytoplasmic IDRs in Bacillus subtilis are required for cell wall homeostasis. The B. subtilis sigma(I) transcription factor is activated in response to envelope stress through regulated intramembrane proteolysis (RIP) of its membrane-anchored anti-sigma factor, RsgI. Unlike canonical RIP pathways, we show that ectodomain (site-1) cleavage of RsgI is constitutive, but the two cleavage products remain stably associated, preventing intramembrane (site-2) proteolysis. The regulated step in this pathway is their dissociation, which is triggered by impaired cell wall synthesis and requires RsgI's extracytoplasmic IDR. Intriguingly, the major peptidoglycan polymerase PBP1 also contains an extracytoplasmic IDR, and we show that this region is important for its function. Disparate IDRs can replace the native IDRs on both RsgI and PBP1, arguing that these unstructured regions function similarly. Our data support a model in which the RsgI-sigma(I) signaling system and PBP1 represent complementary pathways to repair gaps in the PG meshwork. The IDR on RsgI senses these gaps and activates sigma(I), while the IDR on PBP1 directs the synthase to these sites to fortify them. In this study, Brunet et al. investigated the roles of intrinsically disordered protein regions (IDRs) in bacteria, and report that extracytoplasmic IDRs in Bacillus subtilis are required for cell wall homeostasis. Their data support a model in which the IDR on anti-sigma factor RsgI senses gaps in the PG meshwork and activates sigma(I), while the IDR on PBP1 directs the synthase to these sites to fortify them.

Automated summary

In this study, the roles of intrinsically disordered protein regions (IDRs) in bacteria were investigated, and it was reported that extracytoplasmic IDRs in Bacillus subtilis are required for cell wall homeostasis. The data support a model in which the IDR on anti-sigma factor RsgI senses gaps in the PG meshwork and activates sigma(I), while the IDR on PBP1 directs the synthase to these sites to fortify them.