CtpB Assembles a Gated Protease Tunnel Regulating Cell-Cell Signaling during Spore Formation in Bacillus subtilis
| Autor: | Mastny, M, Heuck, A, Kurzbauer, R, Heiduk, A, Boisguerin, P, Volkmer, R, Ehrmann, M, Rodrigues, CDA, Rudner, DZ, Clausen, T |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cell 155(3), 647-658 (2013). doi:10.1016/j.cell.2013.09.050 Cell |
| Popis: | Summary 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. Graphical Abstract Highlights • The CtpB fold composes a narrow protease tunnel gated by a PDZ domain • Substrate binding induces opening of the PDZ gate and protease activation • SpoIVB and CtpB signaling proteases act in a sequential and concerted fashion • SpoIVB and CtpB establish a RIP mechanism to integrate multiple cellular signals Bacterial sporulation depends on cleavage of a membrane-bound inhibitor by CtpB, a protease gated by its own PDZ domain. Substrate recognition leads to a conformational change in CtpB that activates the enzyme and allows access to the active site, thereby restricting proteolysis to a specific substrate. |
| Databáze: | OpenAIRE |
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