A short helix regulates conversion of dimeric and 24-meric ferritin architectures.

The inter-subunit interaction at the protein interfaces plays a key role in protein self-assembly, through which enabling protein self-assembly controllable is of great importance for preparing the novel nanoscale protein materials with unexplored properties. Different from normal 24-meric ferritin, archaeal ferritin, Thermotoga maritima ferritin (TmFtn) naturally occurs as a dimer, which can assemble into a 24-mer nanocage induced by salts. However, the regulation mechanism of protein self-assembly underlying this phenomenon remains unclear. Here, a combination of the computational energy simulation and key interface reconstruction revealed that a short helix involved interactions at the C interface are mainly responsible for the existence of such dimer. Agreeing with this idea, deletion of such short helix of each subunit triggers it to be a stable dimer, which losses the ability to reassemble into 24-meric ferritin in the presence of salts in solution. Further support for this idea comes from the observation that grafting a small helix from human H ferritin onto archaeal subunit resulted in a stable 24-mer protein nanocage even in the absence of salts. Thus, these findings demonstrate that adjusting the interactions at the protein interfaces appears to be a facile, effective approach to control subunit assembly into different protein architectures.