Extended Data Fig. 8: Opportunities and limitations of designs using fusion of multiple distinct oligomers.

a Functional motifs can be affixed upon oligomeric proteins. Cyclic homo-oligomers enable presentation of motifs with high valency, whereas heterodimers enable presentation of two distinct functional motifs in conjunction. Heterotrimers extend such possibilities by enabling the presentation of three distinct motifs at a time. b Heterotrimers can provide an increase in valency while also presenting multiple distinct motifs in conjunction by splicing motifs two of their chains, while joining the third chain to a symmetric homo-oligomer. Additionally, the number of distinct motifs that can be presented by these constructs can be increased further by fusing multiple heterotrimers to a central heterodimer, or another central heterotrimer. c The geometries resulting from fusion of two symmetric homo-oligomers are limited to regular polyhedral groups (nanocages) or wallpaper groups (2D lattices), as defined by the point-symmetries of their constituent interfaces and the angle between symmetry axes. When using heterodimers to create higher order assemblies through rigid fusion, two fusion-accessible termini are used up with each splice step, limiting the range of designs to chains or rings. In contrast, higher ordered assemblies made through fusion of two or more heterotrimers are not limited to the geometric constraints of homo-oligomers or branching constraints of heterodimers; each rigid fusion step leaves a net increase in the number of fusion-accessible chains, enabling extensive opportunities for subsequent splicing. d The iterative fusion of many distinct heterotrimers enables exploration of many new asymmetric constructs, and extensively branching designs that can incorporate many distinct domains. While heterotrimers can be combined with homo-oligomers to create branching symmetric designs, the design of extensively branching asymmetric designs is an avenue that can only be explored using heterotrimeric building blocks.