Finite and extended natural protein assemblies. a) Examples of finite protein assemblies: Interleukin-5 (i, PDB ID: 1HUL), hemoglobin (ii, PDB ID: 1HHO), insulin (iii, PDB ID: 1ZNI), human heavy chain ferritin (iv, PDB ID: 6B8F), and photosystem II (v, PDB ID: 1AXT). b) Examples of extended protein assemblies: 1D actin filament (vi, PDB ID: 6BNO), 2D S-layer (vii, PDB ID: 5N8P) and 3D infectious cytoplasmic polyhedrosis virus protein crystal (viii, PDB ID: 2OH5). c) Close-up views of protein-protein interfaces of interleukin-5 (ix), insulin (x), and ferritin (xi) highlighting non-covalent, covalent, and metal-mediated interactions. In addition to these enthalpic contributions, the expulsion of waters upon the burial of interfacial amino acid residues (i.e., the “hydrophobic effect”) represents an important entropic contribution to interface stability.