Protein cages as building blocks for superstructures

Abstract

Proteins naturally self-assemble to function. Protein cages result from the self-assembly of multiple protein subunits that interact to form hollow symmetrical structures with functions that range from cargo storage to catalysis. Driven by self-assembly, building elegant higher-order superstructures with protein cages as building blocks has been an increasingly attractive field in recent years. It presents an engineering challenge not only at the molecular level but also at the supramolecular level. The higher-order constructs are proposed to provide access to diverse functional materials. Focussing on design strategy as a perspective, current work on protein cage supramolecular self-assembly are reviewed from three principles that are electrostatic, metal-ligand coordination and inherent symmetry. The review also summarises possible applications of the superstructure architecture built using modified protein cages.

Keywords: molecular biophysics; proteins; self‐assembly.

FIGURE 1

Overview of the assembly processes resulting in protein cage superstructures. Protein subunits self‐assemble into protein cage of 0D. Engineering of the exterior surface of the protein cages drive the formation of superstructures across different length scales resulting in 0D, 1D, 2D, and 3D structures

FIGURE 2

Supramolecular assemblies of protein cages based on electrostatic interactions. (a) Photosensitive dendron–CCMV complexes [13]. (b) Temperature‐switchable assembly with CCMV and copolymer, adapted with permission from [14]. (c) Three‐dimensional binary nanoparticle superlattices using CCMV and ferritin with 1‐pentanethiol‐stabilised gold nanoparticles (AuNPs) [15]. (d) Binary assembly of CCMV and avidin [12]. (e) Cocrystals from supercharged fusion peptides and protein cages [16]. CCMV, cowpea chlorotic mottle virus. All figures are adapted with permissions. Figures 2, 3, 4 adapted copyrighted figures from references [12, 13, 14, 15, 16], [17, 18, 19], [20, 21, 22] and have obtained permission to use the materials

FIGURE 3

Supramolecular assemblies of protein cages based on metal‐ligand coordination. (a) 3D ternary crystal of the body‐centred cubic (bcc) arrangement via zinc‐protein coordination [17]. (b) Ferritin−MOFs with the bcc structure [18]. (c) The assembly tunable between a unitary structure and a binary structure [19]. 3D, three‐dimensional; MOF, metal‐organic framework. All figures are adapted with permissions. Figures 2, 3, 4 adapted copyrighted figures from references [12, 13, 14, 15, 16], [17, 18, 19], [20, 21, 22] and have obtained permission to use the materials

FIGURE 4

Supramolecular assemblies of protein cages based on inherent symmetry. (a) 2D and 3D protein superlattices via π–π stacking interactions [21]. (b) 2D and 3D protein arrays driven by hydrophobic interactions [20]. (c) Binary protein–metal crystalline framework [22]. 2D, two‐dimensional; 3D, three‐dimensional. All figures are adapted with permissions. Figures 2, 3, 4 adapted copyrighted figures from references [12, 13, 14, 15, 16], [17, 18, 19], [20, 21, 22] and have obtained permission to use the materials