Supramolecular assembly of protein building blocks: from folding to function

Abstract

Several phenomena occurring throughout the life of living things start and end with proteins. Various proteins form one complex structure to control detailed reactions. In contrast, one protein forms various structures and implements other biological phenomena depending on the situation. The basic principle that forms these hierarchical structures is protein self-assembly. A single building block is sufficient to create homogeneous structures with complex shapes, such as rings, filaments, or containers. These assemblies are widely used in biology as they enable multivalent binding, ultra-sensitive regulation, and compartmentalization. Moreover, with advances in the computational design of protein folding and protein-protein interfaces, considerable progress has recently been made in the de novo design of protein assemblies. Our review presents a description of the components of supramolecular protein assembly and their application in understanding biological phenomena to therapeutics.

Keywords: Protein design; Protein folding; Protein–protein interaction; Supramolecular assembly.

Fig. 1

Statistical analysis of annually defined structure in Protein Data Bank (PDB) (Data obtained from https://www.rcsb.org/stats)

Fig. 2

Schematic image for description of three components of supramolecular protein assembly

Fig. 3

Representative example of folding unit: α-helix, β-sheet, and α/β mixed structure

Fig. 4

Schematic image of symmetric oligomeric building blocks and example two-component assembled structure. A Illustration of point group symmetries. B Representative example of octahedral symmetry constructed by combining C3 trimer and C4 tetramer (left), p6 symmetry constructed by combining C3 trimer and C6 hexamer (middle), and p422 symmetry assembled by combining D2 tetramer and D4 octamer (right) (Image reprinted with permission from Ref [38])

Fig. 5

Various assembled structure and their folding unit of supramolecular protein assembly

Fig. 6

Schematic image of application of a nanocage. A The ferritin nanocages displaying EV71 antigens on the surface as epitopes for the use of vaccine. B The BG505 SOSIP displaying de novo designed icosahedral nanocage. C The octahedral (up) and icosahedral (down) antibody nanocages with fusion of angiopoietin-1 F-domain (A1F) and Fc (Image reprinted with permission from Ref [135, 196, 203])

Fig. 7

Example of enzymatic supramolecular structure via metal coordinate interaction (Image reprinted with permission from Ref [34])

Fig. 8

Example of supramolecular protein assembly with carbon material A single-wall carbon nanotube, B C60 fullerene, and C pristine graphene (Image reprinted with permission from Ref [240, 243, 248])