Spo0F

Spo0F is a small cytosolic response regulator that functions as an essential phosphotransfer intermediary in the initiation of sporulation in Bacillus subtilis and other endospore-forming bacteria. It belongs to the phosphorelay system that transduces environmental and nutritional cues to the master regulator Spo0A. In the canonical pathway, sensor histidine kinases such as KinA through KinE autophosphorylate and transfer phosphate to Spo0F, generating Spo0F∼P. Spo0F then donates the phosphate to the histidine phosphotransferase Spo0B, which in turn transfers it to Spo0A, forming Spo0A∼P that activates a transcriptional program leading to sporulation. Spo0F therefore acts as a receiver protein with no DNA-binding activity and facilitates information flow between the kinases and Spo0A.

Structurally Spo0F is composed primarily of a receiver (REC) domain of about 120–130 amino acids containing the conserved aspartate that accepts the phosphate (the phosphorylation site is typically Asp56 in Bacillus Spo0F). Phosphorylation of Spo0F is magnesium-dependent and reversible, and its steady-state level is controlled by both kinase activity and phosphatases such as the Rap family and Spo0E that dephosphorylate components of the relay. Because Spo0A∼P thresholds regulate sporulation decision, Spo0F function is essential for proper timing and efficiency of spore formation. Spo0F homologs are found in Bacillales and related bacteria that use similar phosphorelays, reflecting a conserved mechanism for integrating signals into Spo0A activation.