CtpB Assembles a Gated Protease Tunnel Regulating Cell-Cell Signaling during Spore Formation in Bacillus subtilis

Mastny, Markus; Heiduk, Anja; Heuck, Alexander; Rudner, David Z.; Clausen, Tim; Rodrigues, Christopher D. A.; Volkmer, Rudolf; Kurzbauer, Robert; Boisguerin, Prisca; Ehrmann, Michael

doi:10.1016/j.cell.2013.09.050

Journal Article

DESY-2014-02420

CtpB Assembles a Gated Protease Tunnel Regulating Cell-Cell Signaling during Spore Formation in Bacillus subtilis

Mastny, M. (Corresponding Author) ; Heuck, A.Extern* ; Kurzbauer, R. ; Heiduk, A. ; Boisguerin, P. ; Volkmer, R. ; Ehrmann, M. ; Rodrigues, C. A. ; Rudner, D. ; Clausen, T.Extern*

2013
Cell Press [Cambridge, Mass.]

Cell 155(3), 647 - 658 (2013) [10.1016/j.cell.2013.09.050]

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Please use a persistent id in citations: doi:10.1016/j.cell.2013.09.050 doi:10.3204/DESY-2014-02420

Abstract: Spore formation in Bacillus subtilis relies on a regulated intramembrane proteolysis (RIP) pathway that synchronizes mother-cell and forespore development. To address the molecular basis of this SpoIV transmembrane signaling, we carried out a structure-function analysis of the activating protease CtpB. Crystal structures reflecting distinct functional states show that CtpB constitutes a ring-like protein scaffold penetrated by two narrow tunnels. Access to the proteolytic sites sequestered within these tunnels is controlled by PDZ domains that rearrange upon substrate binding. Accordingly, CtpB resembles a minimal version of a self-compartmentalizing protease regulated by a unique allosteric mechanism. Moreover, biochemical analysis of the PDZ-gated channel combined with sporulation assays reveal that activation of the SpoIV RIP pathway is induced by the concerted activity of CtpB and a second signaling protease, SpoIVB. This proteolytic mechanism is of broad relevance for cell-cell communication, illustrating how distinct signaling pathways can be integrated into a single RIP module.

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