Structural basis for the differential regulatory roles of the PDZ domain in C-terminal processing proteases

Chueh, C.-K.; Som, N.; Ke, L.-C.; Ho, M.-R.; Reddy, M.; Chang, C.-I.

doi:10.1101/621037

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bioRxiv · 10.1101/621037

Structural basis for the differential regulatory roles of the PDZ domain in C-terminal processing proteases

Chueh, C.-K.·Som, N.·Ke, L.-C.·Ho, M.-R.·Reddy, M.·Chang, C.-I.

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Abstract

Carboxyl (C)-terminal processing proteases (CTPs) participate in protective and regulatory proteolysis in bacteria. The PDZ domain is central to the activity of CTPs but plays inherently different regulatory roles. For example, the PDZ domain inhibits the activity of the signaling protease CtpB by blocking the active site but is required for the activation of Prc (or Tsp), a tail-specific protease that degrades the ssrA-tagged proteins. Here, by structural and functional analysis we show that in the unliganded resting state of Prc, the PDZ domain is docked inside the bowl-shaped scaffold without contacting the active site, which is kept in a default misaligned conformation. In Prc, a hydrophobic substrate sensor distinct from CtpB engages substrate binding to the PDZ domain and triggers a structural remodeling to align the active site residues. Therefore, this work reveals the structural basis for understanding the contrasting roles of the PDZ domain in the regulation of CTPs.

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Chueh, C.-K., Som, N., Ke, L.-C., Ho, M.-R., Reddy, M., Chang, C.-I.. 2019-04-27. Structural basis for the differential regulatory roles of the PDZ domain in C-terminal processing proteases. https://doi.org/10.1101/621037

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