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9.B.174 The Two Tunnel Gated C-terminal Processing Protease (CTP) Family

Spore formation in Bacillus subtilis relies on a regulated intramembrane proteolysis (RIP) pathway that synchronizes mother-cell and forespore development. This is the SpoIV transmembrane signaling pathway (Ding et al., 2013). Crystal structures of the activating protease, CtpB, reflecting distinct functional states, showed 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 (Mastny et al. 2013).

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 (Ding et al., 2013).


References associated with 9.B.174 family:

Ding D., Salvi R. and Roth JA. (2014). Cellular localization and developmental changes of the different isoforms of divalent metal transporter 1 (DMT1) in the inner ear of rats. Biometals. 27(1):125-34. 24318355
Mastny, M., A. Heuck, R. Kurzbauer, A. Heiduk, P. Boisguerin, R. Volkmer, M. Ehrmann, C.D. Rodrigues, D.Z. Rudner, and T. Clausen. (2013). CtpB assembles a gated protease tunnel regulating cell-cell signaling during spore formation in Bacillus subtilis. Cell 155: 647-658. 24243021
Miljkovic, M., G. Uzelac, N. Mirkovic, G. Devescovi, D.B. Diep, V. Venturi, and M. Kojic. (2016). LsbB bacteriocin interacts with the third transmembrane domain of the YvjB receptor. Appl. Environ. Microbiol. [Epub: Ahead of Print] 27342562
Singh, S.K., S. Parveen, L. SaiSree, and M. Reddy. (2015). Regulated proteolysis of a cross-link-specific peptidoglycan hydrolase contributes to bacterial morphogenesis. Proc. Natl. Acad. Sci. USA 112: 10956-10961. 26283368