Cara Vaughan

Research in my lab focuses on the molecular chaperone Hsp90. Hsp90 works in large macromolecular complexes, together with cochaperones, to activate and assemble a multitude of client proteins and protein complexes involved in many signalling pathways. As a consequence it is a key therapeutic target in cancer, neurodegenerative and protein folding diseases.

The role of essential cochaperones in facilitating Hsp90 interactions with substrate proteins

In this project we study the role of the cochaperone Sgt1 and its interaction with Hsp90 in facilitating the assembly of a yeast kinetochore complex, CBF3. The kinetochore is a mega-Dalton protein assembly that bridges between sister chromatids and the microtubules of the spindle pole during mitosis. CBF3 associates with the centromere DNA of S. cerevisiae and is the foundation of kinetochore formation. To this end we are currently assembling early and late intermediates of the CBF3 assembly for structural determination by cryo-EM.

Post Translational Modification of Essential Hsp90 Cochaperones in Chaperone Regulation

Post translational modification of Hsp90 and its cochaperones is an important layer of regulation of Hsp90 function. We are focusing on the structural characterisation of the conformational changes caused by phosphorylation and dephosphorylation of the cochaperone Cdc37. Cdc37 is a kinase-specific adaptor of Hsp90, and we are particularly interested in its interaction with the Hsp90-dependent phosphatase PP5, which is essential for kinase activation. This will enable us to define at high resolution the individual complexes present during the pathway of kinase activation by Hsp90 and Cdc37.

Techniques

The techniques we use include X-ray crystallography and single particle cryo-electron microscopy, in addtion to other biophysical and biochemical techniques to complement structural studies. We also collaborate with Prof Chris Kay, UCL, to use EPR spectroscopy.

ISMB Lecturer in Structural Biology

phone: +44 (0)20 7631 6809

c.vaughan@mail.cryst.bbk.ac.uk

School of Crystallography
Birkbeck College
Malet Street

London, WC1E 7HZ