Structural symmetry and protein function

The majority of soluble and membrane-bound proteins in modem cells are symm etrical oligomeric complexes with two or more subunits. The evolutionary se lection of symmetrical oligomeric complexes is driven by functional, geneti c, and physicochemical needs. Large proteins are selected for specific morp hological functions, such as formation of rings, containers, and filaments, and for cooperative functions, such as allosteric regulation and multivale nt binding. Large proteins are also more stable against denaturation and ha ve a reduced surface area exposed to solvent when compared with many indivi dual, smaller proteins. Large proteins are constructed as oligomers for rea sons of error control in synthesis, coding efficiency, and regulation of as sembly. Symmetrical oligomers are favored because of stability and finite c ontrol of assembly. Several functions limit symmetry, such as interaction w ith DNA or membranes, and directional motion. Symmetry is broken or modifie d in many forms: quasisymmetry, in which identical subunits adopt similar b ut different conformations; pleomorphism, in which identical subunits form different complexes; pseudosymmetry, in which different molecules form appr oximately symmetrical complexes; and symmetry mismatch, in which oligomers of different symmetries interact along their respective symmetry axes. Asym metry is also observed at several levels. Nearly all complexes show local a symmetry at the level of side chain conformation. Several complexes have re ciprocating mechanisms in which the complex is asymmetric, but, over time, all subunits cycle through the same set of conformations. Global asymmetry is only rarely observed. Evolution of oligomeric complexes may favor the fo rmation of dimers over complexes with higher cyclic symmetry, through a mec hanism of pre-positioned pairs of interacting residues. However, examples h ave been found for all of the crystallographic point groups, demonstrating that functional need can drive the evolution of any symmetry.