The PDZ domain of the SpoIVB transmembrane signaling protein enables cis-trans interactions involving multiple partners leading to the activation of the pro-sigmaK processing complex in Bacillus subtilis.

In sporulating cells of Bacillus subtilis, the serine peptidase SpoIVB is the essential component of a transmembrane signaling cascade between the two intracellular compartments (forespore and mother cell) that leads to activation of the sigmaK transcription factor in the mother cell chamber. This regulatory process, referred to as the sigmaK checkpoint, is essential for ensuring proper development of the spore and introduces an appropriate level of fidelity to the developmental process. This work unravels the signaling process and establishes how SpoIVB interacts with other protein partners in the sigmaK checkpoint. SpoIVB is synthesized as a zymogen that is autoproteolytically activated and carries a PDZ domain that is responsible for at least three distinct binding reactions, a phenomenon not previously demonstrated for an individual PDZ domain. First, binding to the SpoIVB NH2 terminus to maintain the protein in its zymogen form. Second, following secretion across a spore membrane, binding in trans to the COOH terminus of another SpoIVB molecule. Binding in trans facilitates the first cleavage event of SpoIVB near the NH2 terminus releasing it from the inner forespore membrane. We show that at least two further cis cleavage events occur at specific sites near the NH2 terminus after which the PDZ domain targets SpoIVB to the pro-sigmaK processing complex in the outer forespore membrane. Specifically, SpoIVB binds to the COOH terminus of BofA. In turn, this allows SpoIVB to cleave the COOH terminus of SpoIVFA an event pivotal to activating the SpoIVFB zinc metalloprotease by disruption of the heteroligomeric pro-sigmaK complex.