Investigation of the structural and biochemical properties of mammalian tolloid proteinases

The family of BMP1/Tolloid-like proteases (B/TPs) is involved in a variety of important functions in mammalian tissue development. Firstly, B/TPs cut collagen precursors to allow their assembly in the extra-cellular matrix (ECM).

Mutations or a loss of function of B/TPs result in several developmental defects or can result in death during the embryonic stage. The second role of B/TPs is activating different growth factors.

These messenger molecules are involved in communicating with cells during the formation of different tissues, including bones and the brain. Our work aims to understand how B/TPs carry out their function and how mutations result in diseases.

To do so, we aim to determine the 3-dimensional structure of two members of the B/TP family using cryogenic electron microscopy. Furthermore, we want to understand how B/TPs interact with their substrates, as well as known effector proteins.

We hope our results will allow for a better understanding of B/TP function and regulation and provide potential basis for therapeutic approaches for B/TP-associated diseases.