Studying the conformational landscape of P97, an essential ATPase

The ATPase p97 has essential roles in many cellular processes. A better understanding of its different structures could reveal more about these functions.

The goals of this research project are to:

1. Characterise the full conformational landscape of isolated p97 complexes using cryo-electron tomography (cryo-ET).
2. Characterise the various complexes that p97 assembles in cells using cryo-ET.
3. Combine the conformational landscapes obtained for isolated p97 complexes and p97 in cells.

The details

ATPases are enzymes that use the energy released from ATP hydrolysis to perform other functions in the cell. The ATPase p97 uses this energy to remove other proteins from large complexes or assemblies. This function is an important part of many cellular processes.

Analysis using single-particle cryo-electron microscopy shows that p97 exists in different conformations. The protein interacts with up to 20 cofactors, which target its function to different pathways in the cell. But the spatial and dynamic properties of these interactions remain unknown.

This project aims to characterise these properties and the p97 conformational landscape. This knowledge will be vital to understanding the protein’s functional mechanisms.

Supervision team

The University of Melbourne: Associate Professor Isabelle Rouiller

CNRS, Sorbonne Université: Dr Slavica Jonic