Jacqui Gulbis-Projects

Jacqui Gulbis-Projects



Mechanisms controlling ion permeation in potassium channels

Potassium conduction across cell membranes occurs through the highly selective pore of K+ channels, and is regulated by cellular and electrical signals. The flow of ions through the permeation pathway is controlled by means of molecular ‘gates’.

Our objective is to determine the nature of these gate(s) and pin down mechanisms that cause the channel to switch between conducting and non-conducting states. Our initial study unexpectedly revealed a correlation between conduction status and subtle conformational changes in an intracellular assembly. We are following this up with evidence of interdependent gating processes controlling ion permeation.

Space filling representation of a Kir potassium channel assembly

Protein translocation to the mitochondria

About 30 per cent of cellular proteins are found in membranes. In eukaryotic cells, mitochondrial membrane proteins undergo a sequence of chaperoned transfers across a double- membrane system utilising dedicated mitochondrial translocases.

The targeting and transfer of membrane-spanning transporters through the intermembrane space requires specialised translocase components. Our structures of Tim9-Tim10 revealed a modular propeller-like fold, suggesting a previously unanticipated mode of chaperone activity and serving as a model for deriving function. Our objective is to experimentally define the interactions of mitochondrial carrier precursors with translocase components and to look at how translocase components co-assemble. 

Alternate views of Tim9-Tim10 showing its large central cavity (left).
A pair of Tim9-Tim10 complexes form a larger assembly (right).