Protein Quaternary Structure: Symmetry Patterns


Protein molecules can assemble into larger, multisubunit oligomers that possess unique quaternary structures and biological properties. The properties of the oligomeric protein can be quite different from those of the individual subunits. The noncovalent protein–protein interactions giving rise to oligomers often result in symmetric complexes containing identical monomers in identical environments. The symmetry properties of these complexes are described, in particular with respect to the types of subunit–subunit interactions giving rise to the oligomers. Because the symmetry of the macromolecular assemblies is based on the symmetric interactions between the subunits, understanding the symmetry provides further insight into the functioning of the oligomers. Specific examples presented include: dimers and heptamers with cyclic symmetry, tetrameric and octameric oligomers with dihedral symmetry, multienzyme complexes with tetrahedral and dodecahedral structures, and pilin helical oligomers.

Key Concepts:

  • Many proteins form large complexes made up of multiple copies of identical subunits.

  • Analysis of the quaternary structures of protein complexes in terms of symmetry can determine how equivalent the subunits are, in function as well as structure.

  • Subunits in dimeric proteins related by twofold rotation axes interact using the same functional groups on each subunit, that is, isologously.

  • Protein complexes showing cyclic and helical symmetries have subunits that do not interact with the same functional groups on each subunit; they interact heterologously.

  • Large protein complexes can take on the symmetries shown by the Platonic solids.

  • Helical symmetry is found in large rod‐like structures such as pili.

  • Protein complexes showing point group symmetry are constructed using all of the available subunit–subunit binding surfaces and are ‘closed’ to addition of further subunits.

  • Helical structures containing identical subunits have unoccupied binding surfaces at the termini of the helix that can bind additional subunits and grow into unlimited polymers.

Keywords: quaternary structure; symmetry; viruses; multienzyme complexes; protein–protein interactions; protein oligomers

Figure 1.

Glutathione S‐transferase dimer (Protein Data Bank entry 1K3Y). (a) A view of the dimer showing atoms as space‐filling spheres (carbon atoms in grey, oxygen atoms in red, nitrogen atoms in blue and hydrogen atoms omitted). (b) The same view with the carbon atoms in one subunit coloured light blue and in the other subunit pink. (c) The two subunits are shown in a cartoon denoting the path of the linear polypeptide chain making up the protein. α helices and β strands are connected by coiled regions. The twofold rotation axis relating the two subunits is perpendicular to the plane of the figure, and its location is denoted by the bold‐faced 2. Figure drawn with Molscript (Kraulis, ) and Raster3d (Merritt and Bacon, ).

Figure 2.

Hemolysin, a heptameric integral membrane protein (Protein Data Bank entry 7AHL). (a) Cartoon showing the structure of an isolated subunit. (b) The complete, functional protein contains seven identical subunits related by a sevenfold rotation axis (denoted by the line and bold‐faced 7). (c) The heptamer rotated 90° from the view in (c). The sevenfold axis is perpendicular to the plane of the figure and is located in the centre of the pore formed by the seven subunits. Figure drawn with Molscript and Raster3d.

Figure 3.

Streptavidin, a tetrameric protein showing 222 symmetry (Protein Data Bank entry 3RY2). Subunits are shown in yellow, red, cyan and green. The view is along one of the twofold axes (denoted by the central bold‐faced 2) showing the relationship between the red and cyan subunits and between the yellow and green subunits. Two other twofold axes lie in the plane of the figure and are denoted by lines and 2. Figure drawn with Molscript and Raster3d.

Figure 4.

An octameric oxygen‐binding protein, hemerythrin (Protein Data Bank entry 1HMO). (a) Four subunits related by a fourfold rotation axis (4) form a layer of subunits. (b) Another layer of four subunits, flipped over relative to that shown in (a). (c) In the complete octamer, one subunit from the layer shown in (a), the red one, overlaps two subunits from the other layer and is related to them by the two twofold rotation axes shown in the frame. (d) The complete octamer and its fourfold and twofold rotation axes. Figure drawn with Molscript and Raster3d.

Figure 5.

The Platonic solids and their rotational symmetry elements. (a) The tetrahedron possesses threefold axes passing through each vertex and its opposite face. There are also twofold rotation axes perpendicular to each pair of opposite edges. Each tetrahedron contains four threefold axes and three twofold axes. Only one example of each is shown for simplicity in each of the figures. (b) The cube possesses fourfold axes perpendicular to the square faces, threefold axes along each body diagonal and twofold axes perpendicular to each set of opposite edges. (c) The octahedron contains the same symmetry elements, but with the fourfold axes passing through opposite vertices, the threefold axes perpendicular to each pair of triangular faces and twofold axes perpendicular to pairs of opposite edges. (d) The dodecahedron possesses fivefold axes perpendicular to each pentagonal face, threefold axes passing through opposite vertices and twofold axes perpendicular to pairs of opposite edges. (e) The icosahedron possesses fivefold axes through opposite vertices, threefold axes perpendicular to the triangular faces and twofold axes perpendicular to opposite edges. Figure drawn with XtalView (McRee, ) and Raster3d.

Figure 6.

3‐Dehydroquinase forms a complex containing 12 subunits with tetrahedral symmetry (Protein Data Bank entry 1J2Y). (a) Three subunits form a triangular‐shaped structure with a threefold rotation axis (3) relating the subunits. (b) Two trimeric sets, blue and pink, are related by a twofold rotation axis midway between their threefold axes. (c) Combination with two more sets of three subunits (yellow and grey) produces a complex containing all of the rotational symmetry of a tetrahedron. Figure drawn with Molscript and Raster3d.

Figure 7.

Dihydrolipoyl transacetylase, the core structure of pyruvate dehydrogenase (Protein Data Bank entry 1B5S). (a) General view of the 60 subunits making up the core with dodecahedral symmetry. (b) Looking down the fivefold axis, five subunits are coloured in yellow to show how they are related by the fivefold rotation axis. (c) Looking down a threefold rotation axis, the blue subunits are related by the threefold. The threefold axis applies to the entire particle, not just the coloured ones used to demonstrate the rotational symmetry. (d) Looking down a twofold axis. Figure drawn with Molscript and Raster3d.

Figure 8.

The type IV pilus from Neisseria gonorrhoeae (Protein Data Bank entry 2HIL). (a) Several subunits making up this model of the pilus are shown in cartoon mode. One subunit is shown in space‐filling mode (red). (b) An orange subunit is related to the red one by a vertical helical axis. A yellow subunit is related to the orange one by the same helical axis (c), as is a green subunit related to the yellow one (d). (e) The complete model is shown in space‐filling mode. Figure drawn with Molscript and Raster3d.



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Further Reading

Caspar DLD and Klug A (1962) Physical principles in the construction of regular viruses. Cold Spring Harbor Symposia on Quantitative Biology 27: 1–24.

Cotton FA (1990) Chemical Applications of Group Theory. New York, NY: Wiley.

Goodsell DS and Olson AJ (2000) Structural symmetry and protein function. Annual Review of Biophysics and Biomolecular Structure 29: 105–153.

Hargittai I and Hargittai M (1994) Symmetry: A Unifying Concept. Bolinas, CA: Shelter Publications.

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How to Cite close
Stenkamp, Ronald E(Apr 2014) Protein Quaternary Structure: Symmetry Patterns. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0003121.pub3]