Designed Two- and Three-Dimensional Protein Nanocage Networks Driven by Hydrophobic Interactions Contributed by Amyloidogenic Motifs.

Precise manipulation of protein self-assembly by noncovalent interactions into programmed networks to mimic naturally occurring nanoarchitectures in living organisms is a challenge due to its structural heterogeneity, flexibility, and complexity. Herein, by taking advantage of both the hydrophobic forces contributed by the "GLMVG" motif, a kind of amyloidogenic motif (AM), and the high symmetry of protein nanocages, we have built an effective protein self-assembly strategy for the construction of two-dimensional (2D) or three-dimensional (3D) protein nanocage arrays. According to this strategy, "GLMVG" AMs from β-amyloid 42 were grafted onto the outer surface of a 24-mer ferritin nanocage close to its C symmetry channels, initially resulting in the production of subgrade 2D nanocage arrays and ultimately generating 3D highly ordered arrays with a simple cubic packing pattern as the reaction time increases. More importantly, the reversibility and the formation rate of these protein arrays can be modulated by pH. This work provides a de novo design strategy for accurate control over 2D or 3D protein self-assemblies.