Structural Symmetry and Protein Function

Abstract

The majority of soluble and membrane-bound proteins in modern cells are symmetrical oligomeric complexes with two or more subunits. The evolutionary selection of symmetrical oligomeric complexes is driven by functional, genetic, and physicochemical needs. Large proteins are selected for specific morphological functions, such as formation of rings, containers, and filaments, and for cooperative functions, such as allosteric regulation and multivalent binding. Large proteins are also more stable against denaturation and have a reduced surface area exposed to solvent when compared with many individual, smaller proteins. Large proteins are constructed as oligomers for reasons of error control in synthesis, coding efficiency, and regulation of assembly. Symmetrical oligomers are favored because of stability and finite control of assembly. Several functions limit symmetry, such as interaction with DNA or membranes, and directional motion. Symmetry is broken or modified in many forms: quasisymmetry, in which identical subunits adopt similar but different conformations; pleomorphism, in which identical subunits form different complexes; pseudosymmetry, in which different molecules form approximately symmetrical complexes; and symmetry mismatch, in which oligomers of different symmetries interact along their respective symmetry axes. Asymmetry is also observed at several levels. Nearly all complexes show local asymmetry at the level of side chain conformation. Several complexes have reciprocating 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 formation of dimers over complexes with higher cyclic symmetry, through a mechanism of prepositioned pairs of interacting residues. However, examples have been found for all of the crystallographic point groups, demonstrating that functional need can drive the evolution of any symmetry.

Thermal dissociation of the protein homodimer ecotin in the gas phase

“…In contrast, the charge distribution has no measurable effect on the dissociation kinetics and energetics of the E 2 17ϩ dimer. (J Am Soc Mass Spectrom 2002, 13, 1432-1442) © 2002 American Society for Mass Spectrometry P rotein complexes composed of two or more subunits are believed to constitute the bulk of soluble and membrane-bound proteins [1,2]. While the importance of protein assemblies in cellular function is well recognized, their structural characterization remains a significant analytical challenge.…”

Asymmetric perturbations of signalling oligomers

“…Dimers are the most prevalent oligomers (Goodsell and Olson, 2000). Although most homodimers are symmetric, 1:2 ligand binding (to half of the sites) is usually a source of asymmetry (Miguez, 2010;Swapna et al, 2012).…”

“…Human perception of symmetric objects and structures has subjective and holistic characteristics. Symmetry can be associated with harmony, pleasure, stability (Blundell and Srinivasan, 1996;Goodsell and Olson, 2000;Kojić-Prodić and Štefanić, 2010;Thompson, 1952). In contrast, symmetry violation and asymmetry might seem disharmonic, transient and instable.…”

“…This is obviously a source of emerging structural symmetry (André et al, 2008;Lee and Blaber, 2011;Schulz, 2009). Some of the benefits of symmetric oligomers are greater biosynthetic and folding efficiency; amenability to cooperativity, allosteric regulation and adaptation; stability and reduced aggregation (André et al, 2008;Broom et al, 2012;Goodsell and Olson, 2000).…”

“…Global symmetry is often associated with local binding asymmetry (Goodsell and Olson, 2000). Some specific requirements of signalling oligomers such as rapid and reversible action cannot be reconciled with high stability.…”