Regulatory Proteolysis

PDZ-proteases as versatile sensors in cellular signaling

Proteases carry out a challenging task in the cell as they have to perform protective and regulatory functions in parallel. They are protective when they remove severely damaged proteins and regulatory when they activate specific signaling proteins. To uncover the basic principles of regulatory proteolysis, PDZ-proteases represent a great model system.

PDZ-proteases combine an enzymatic protease with a regulatory PDZ domain, which is a classical protein-protein interaction motif binding to the C-terminus of specific ligands. Most often, PDZ-proteases function as sensor proteins in various signaling pathways. Upon perceiving a specific biological signal, the protease activity is turned on and then stimulates the respective signaling pathway. Importantly, protease activation occurring in a reversible and tightly controlled manner is a unique property of PDZ-proteases.

In this project, we are interested in

  • the intra-molecular communication between PDZ domain and remote proteolytic site.
  • the mechanisms of PDZ-proteases to function as versatile sensor proteins in cellular signaling.
  • the general relevance of PDZ domains as enzymatic co-factors and sensor domains.

Projects in the lab

DegS - engaged with and controlled by stress-signaling peptides
Deg1 - view inside a pH-regulated protease cage
CtpB - featuring a gated protease tunnel for tight RIP control