Fig. 1: Design of symmetry-matched plugs to fill empty symmetry axes in protein nanoparticles.

a, Six de novo tetramers (gray) and 12 dimeric Fc domains (purple) assemble into a porous octahedral O42 nanoparticle. The tetramers are aligned along the four-fold symmetry axis, and the Fc domains along the two-fold symmetry axis. b, Combinations of helical repeat proteins are fused to each other and to the pH trimer subunit at regions of high backbone overlap between pairs of helices to generate fused trimer subunits large enough to fully occupy the void along the three-fold axis in the original nanoparticle. c, The three-fold symmetry axes of the resulting pH-dependent trimeric fusions and the nanoparticle are aligned. Favorable docked arrangements are then generated by sampling rotations and translations along this axis. d, The resulting docked three-component nanoparticles have eight new trimeric plug subunits (yellow) that occupy the three-fold symmetry axes of the octahedral architecture. UCSF ChimeraX 1.6 (ref. ⁵⁴) and the PyMOL Molecular Graphics System version 2.5 (Schrödinger) were used to create a–d.