CtpB assembles a gated protease tunnel regulating cell-cell signaling during spore formation in Bacillus subtilis.
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.
Research Institute of Molecular Pathology, 1030 Vienna, Austria.
Markus
M
Mastny
Alexander
A
Heuck
Robert
R
Kurzbauer
Anja
A
Heiduk
Prisca
P
Boisguerin
Rudolf
R
Volkmer
Michael
M
Ehrmann
Christopher D A
CD
Rodrigues
David Z
DZ
Rudner
Tim
T
Clausen
D000495:Allosteric Site; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000502:physiology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054731:PDZ Domains; D016415:Sequence Alignment; D015398:Signal Transduction; D013171:Spores, Bacterial
D001426:Bacterial Proteins