Researchers from the Walter and Eliza Hall Institute have overturned conventional wisdom on how cell movement across all species is controlled, solving the structure of a protein that cuts power to the cell 'motor'. The protein could be a potential drug target for future malaria and anti-cancer treatments.
By studying the structure of actin-depolymerising factor 1 (ADF1), a key protein involved in controlling the movement of malaria parasites, the researchers have demonstrated that scientists' decades-long understanding of the relationship between protein structure and cell movement is flawed.
Dr Jake Baum and Mr Wilson Wong from the institute's Infection and Immunity division and Dr Jacqui Gulbis from the Structural Biology division, in collaboration with Dr Dave Kovar from the University of Chicago, US, led the research, which appears in today's edition of the Proceedings of the National Academy of Sciences USA.
Dr Baum said actin-depolymerising factors (ADFs) and their genetic regulators have long been known to be involved in controlling cell movement, including the movement of malaria parasites and movement of cancer cells through the body. Anti-cancer treatments that exploit this knowledge are under development.
"ADFs help the cell to recycle actin, a protein which controls critical functions such as cell motility, muscle contraction, and cell division and signaling," Dr Baum said. "Actin has unusual properties, being able to spontaneously form polymers which are used by cells to engage internal molecular motors much like a clutch does in the engine of your car. A suite of accessory proteins control how the clutch is engaged, including those that dismantle or 'cut' these polymers, such as ADF1.
"For many years research in yeast, plants and humans has suggested that the ability of ADFs to dismantle actin polymers effectively disengaging the clutch required a small molecular 'finger' to break th
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Walter and Eliza Hall Institute