Quaternary structure

In protein molecules in a multi-subunit complex.

Description and examples

Many proteins are actually assemblies of more than one allostery in "multimeric" enzymes, that many proteins undergo regulation and perform their physiological function.

The above definition follows a classical approach to biochemistry, established at times when the distinction between a protein and a functional, proteinaceous unit was difficult to elucidate. More recently, people refer to protein-protein interaction when discussing quaternary structure of proteins and consider all assemblies of proteins as protein complexes.

Nomenclature of quaternary structures

The number of subunits in an oligomeric complex are described using names that end in -mer (Greek for "part, subunit"). Formal Greco-Latinate names are generally used for the first ten types and can be used for up to twenty subunits, whereas higher order complexes are usually described by the number of subunits, followed by -meric.

1 = monomer
2 = dimer
3 = trimer
4 = tetramer
5 = pentamer
6 = hexamer

7 = heptamer
8 = octamer
9 = nonamer
10 = decamer
11 = undecamer
12 = dodecamer

13 = tridecamer
14 = tetradecamer
15 = pentadecamer*
16 = hexadecamer
17 = heptadecamer*
18 = octadecamer

19 = nonadecamer
20 = eicosamer
21-mer
22-mer
23-mer*
etc.

*No known examples

Although complexes higher than octamers are rarely observed for most proteins, there are some important exceptions. Viral capsids are often composed of multiples of 60 proteins. Several ribosome is probably the largest molecular machine, and is composed of many RNA and protein molecules.

In some cases, proteins form complexes that then assemble into even larger complexes. In such cases, one uses the nomenclature, e.g., "dimer of dimers" or "trimer of dimers", to suggest that the complex might dissociate into smaller sub-complexes before dissociating into monomers.

Determination of quaternary structure

Protein quaternary structure can be determined using a variety of experimental techniques that require a sample of protein in a variety of experimental conditions. The experiments often provide an estimate of the mass of the native protein and, together with knowledge of the masses and/or stoichiometry of the subunits, allow the quaternary structure to be predicted with a given accuracy. It is not always possible to obtain a precise determination of the subunit composition for a variety of reasons.

The number of subunits in a protein complex can often be determined by measuring the hydrodynamic molecular volume or mass of the intact complex, which requires native solution conditions. For folded proteins, the mass can be inferred from its volume using the partial specific volume of 0.73 ml/g. However, volume measurements are less certain than mass measurements, since unfolded proteins appear to have a much larger volume than folded proteins; additional experiments are required to determined whether a protein is unfolded or has formed an oligomer.

Methods that measure mass of intact complex directly

sedimentation-equilibrium analytical ultracentrifugation
mass spectrometry

Methods that measure the size of the intact complex directly

static light scattering
size exclusion chromatography (requires calibration)

Methods that measure the size of the intact complex indirectly

sedimentation-velocity analytical ultracentrifugation (measures the translational diffusion constant)
dynamic light scattering (measures the translational diffusion constant)
pulsed-gradient protein nuclear magnetic resonance (measures the translational diffusion constant)
fluorescence polarization (measures the rotational diffusion constant)
dielectric relaxation (measures the rotational diffusion constant)

Methods that measure the mass or volume under unfolding conditions (such as cross-linking reagents.

Protein-protein interactions

Proteins are capable of forming very tight complexes. For example, dissociation constant. Other proteins have evolved to bind specifically to unusual moieties on another protein, e.g., biotin groups (avidin), phosphorylated tyrosines (SH2 domains) or proline-rich segments (SH3 domains).