For 50 years, biologists have known that cells build their internal scaffolding from actin filaments, but we've never actually seen how filament formation begins. I'm excited to share that our collaborative team has solved this basic mystery about the cytoskeleton.
Using x-ray crystallography, the Robinson group captured the first atomic-resolution structure of an actin nucleus: the three-molecule complex that starts every actin filament. Their secret weapon? Villin protein from Paralvinella sulfincola, a remarkable worm that thrives in scalding deep-sea thermal vents. Collected by submarine, the worm’s naturally stable actin-binding protein proved perfect for crystallization.
The three actin molecules in the nucleus aren't identical: each adopts a different shape, representing different stages of the transformation from individual units to filament building blocks. They also discovered a molecular gate that dynamically opens and closes to allow new actin molecules to join the growing filament.
The structure also illuminates how actin-binding proteins cut filaments: they exploit natural fluctuations to compete for binding sites and destabilize the structure. This principle likely applies to other actin-binding proteins relevant to disease and development, opening new avenues for intervention.
This work was led by the Robinson group, with contributions from the Girguis (marine biology) and Copley (genomics) groups.
Our paper is out now in Science Advances. https://doi.org/10.1126/sciadv.adw6915
Using x-ray crystallography, the Robinson group captured the first atomic-resolution structure of an actin nucleus: the three-molecule complex that starts every actin filament. Their secret weapon? Villin protein from Paralvinella sulfincola, a remarkable worm that thrives in scalding deep-sea thermal vents. Collected by submarine, the worm’s naturally stable actin-binding protein proved perfect for crystallization.
The three actin molecules in the nucleus aren't identical: each adopts a different shape, representing different stages of the transformation from individual units to filament building blocks. They also discovered a molecular gate that dynamically opens and closes to allow new actin molecules to join the growing filament.
The structure also illuminates how actin-binding proteins cut filaments: they exploit natural fluctuations to compete for binding sites and destabilize the structure. This principle likely applies to other actin-binding proteins relevant to disease and development, opening new avenues for intervention.
This work was led by the Robinson group, with contributions from the Girguis (marine biology) and Copley (genomics) groups.
Our paper is out now in Science Advances. https://doi.org/10.1126/sciadv.adw6915
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