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A protein diagram shows the structure of the malaria parasite protein ADF1 (actin-depolymerizing factor 1) (L) compared to a human ADF (R). The noticeable lack of the 'finger' in malaria parasite ADF1 led researchers to upend the conventional theory of how the protein controlled cell movement. (J. Baum & W. Wong/Walter & Eliza Hall Institute)
The intricate structure of a key cell protein has been revealed, shedding new light on fundamental processes in cell movement, growth, and division, according to a study published in Proceedings of the National Academy of Sciences USA on May 30.
Scientists from the Walter and Eliza Hall Institute in Melbourne, Australia used a subatomic particle accelerator called a synchrotron to capture detailed three-dimensional images of actin-depolymerising factor 1 (ADF1), one of the proteins that controls movement in malaria parasites by stopping power to the cell "motor."
"Imaging the protein structure at such high resolution was critical in proving beyond question the segment of the protein responsible for cutting actin polymers,” said co-author Wilson Wong in a press release.
"ADFs help the cell to recycle actin, a protein which controls critical functions such as cell motility, muscle contraction, and cell division and signaling," co-author Jake Baum explained in the release.
"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,” Baum added. “A suite of accessory proteins control how the clutch is engaged, including those that dismantle or 'cut' these polymers, such as ADF1.”
For decades, research on yeast, plant and human cells suggested ADFs dismantle actin polymers using a small molecular “finger” to break the actin in two, effectively disengaging the clutch, Baum said. However, the synchrotron showed that ADF1 lacks this "finger,” yet can still cut the polymers.
“We discovered that a previously overlooked part of the protein, effectively the 'knuckle' of the finger-like protrusion, was responsible for dismantling the actin; we then discovered this 'hidden' domain was present across all ADFs," Baum said.
Targeting this protein could help in developing drugs for malaria and also anti-cancer treatments.
