One of the main research areas in our lab involves the study of encapsulins - bacterial protein cages that serve as organelles for hosting enzymatic reactions.1 We are using engineered encapsulin cages with different porosities to control the outcomes of encapsulated enzymatic reactions such as carbon fixation.2
Our recent unpublished work on encapsulin enginering has revealed the surprising plasticity of protein self-assembly. In one example, a single point mutant is sufficient to drive a complete structural shift from a canonical icosahedral capsid to an unprecedented tetrahedral assembly that is stabilised by novel protein-protein interactions, as determined by cryo-EM, native mass spectrometry, and mass photometry. In another example, the addition of small fusion domains to encapsulins leads to divergent self-assembly dynamics, ranging from large dynamic assemblies to complete disruption of cage assembly, depending on the choice of fusion partner. These two examples shed new light on how small sequence modifications can lead to major structural and dynamic changes when propagated over a large protein assembly.