Point mutation in a virus-like capsid drives symmetry reduction to form tetrahedral cages.

Viral capsids are cage-like protein assemblies that preferentially adopt icosahedral symmetry to maximise their internal volume for housing genetic material. This icosahedral preference extends to encapsulins, a widespread family of bacterial protein cages which evolved from viral capsids. Counter to this fundamental geometric preference, the formation of well-defined tetrahedral cages from a single amino acid substitution in an encapsulin reveals the surprising geometric flexibility of a common viral protein fold. These findings suggest that protein oligomerisation is far more permissive than intuitively expected, where serendipitous interactions between proteins arising from minimal mutations can cascade to form vast architectural changes. The ability to redesign protein architectures through simple mutations should enable biotechnological advances in vaccine development, drug delivery, and enzymatic biomanufacturing.