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:
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.
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.
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]
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.
Examples:
TC#	Name	Organismal Type	Example
9.B.174.1.1	The C-terminal processing protease, CtpB (YvjB). 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 (Mastny et al. 2013). May show limited sequence similarity with 8.A.24.1.1. The transmembrane domain serves as a receptor for the LsbB bacteriocin in Lactococcus lactis (Miljkovic et al. 2016).	Firmicutes	CtpB of Bacillus subtilis

9.B.174.1.2	Tail-specific protease, Prc or Tsp, of 682 aas and 1 N-terminal TMS. Similar to 9.B.174.1.1 only in the central hydrophilic region. Prc, together with an outer membrane lipoprotein, NlpI, contributes to growth and enlargement of the peptidoglycan sacculus by modulating the cellular levels of the cross-link-cleaving hydrolase, MepS. It thus contributes to growth and enlargement of the PG sacculus (Singh et al. 2015).		Prc of E. coli

9.B.174.1.3	S41 family peptidase of 554 aas and one N-terminal TM		Peptidase of Alistipes finegoldii

9.B.174.1.4	Carboxyl-terminal-processing peptidase 3, chloroplastic of 523 aas and 1 N-terminal TM		Peptidase of Oryza sativa

Examples:
TC#	Name	Organismal Type	Example
9.B.174.2.1	S41 family peptidase of 377 aas with one N-terminal TMS.		*UP of Sphingomonas* sp. 35-24ZXX**

9.B.174.2.2	Uncharacterized protein of 730 aas and 1 N-terminal TMS. Only the C-terminal sequence is similar to other members of this family.		UP of Arsukibacterium ikkense

9.B.174.2.3	Interphotoreceptor retinoid binding protein, partial of 409 aa		Retinoid BP of Abrawayaomys ruschii

9.B.174.2.4	Uncharacterized protein of 458 aas and one N-terminal TMS.		UP of Saccharibacter floricola

9.B.174.2.5	S41 family peptidase of 531 aas and 1 N-terminal TMS.		S41 peptidase of Flavobacterium columnare