De Novo Design of Pseudosymmetric Protein Hetero-Oligomers

Abstract

Protein design success is considerably higher now than it has been in the recent past, but the simultaneous design of many complex interactions, such as hetero-oligomers, remains difficult. We developed a strategy for efficiently designing pseudosymmetric hetero-oligomers by completing a longer series of simpler tasks and created specifically assembling hetero-oligomers. The property of psuedosymmetry could also be leveraged to create protein nanocages with T=4 triangulation numbers, which are prevalent in nature but difficult to design. We start by designing T=1 nanocages with tetrahedral, octahedral, and icosahedral symmetries using symmetric homotrimers, then expand the cages to T=4 through pseudosymmetrization of the component trimers and design of additional interfaces. These approaches highlight the benefits of pseudosymmetry and stepwise approaches to protein material design and represent general avenues for the design of higher complexity structures.