Quaternary structure

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In biochemistry, quaternary structure is the arrangement of multiple folded protein molecules in a multi-subunit complex.

Contents

1 Description and examples
2 Quaternary Structures Nomenclature
3 Determination of quaternary structure
4 Protein-protein interactions
5 See also
6 External links

Description and examples

Many proteins are actually assemblies of more than one polypeptide chain, which in the context of the larger assemblage are known as protein subunits. In addition to the tertiary structure of the subunits, multiple-subunit proteins possess a quaternary structure, which is the arrangement into which the subunits assemble. Enzymes composed of subunits with diverse functions are sometimes called holoenzymes, in which some parts may be known as regulatory subunits and the functional core is known as the catalytic subunit. Examples of proteins with quaternary structure include hemoglobin, DNA polymerase, and ion channels. Other assemblies referred to instead as multiprotein complexes also possess quaternary structure. Examples include nucleosomes and microtubules. Changes in quaternary structure can occur through conformational changes within individual subunits or through reorientation of the subunits relative to each other. It is through such changes, which underlie cooperativity and 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.

Quaternary Structures Nomenclature

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 molecular machines are also found in the cell, such as the proteasome (four heptameric rings = 28 subunits), the transcription complex and the spliceosome. The 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

The number of subunits in a protein complex can often be determined by measuring the hydrodynamic volume or mass under native solution conditions, which may be done by size exclusion chromatography, analytical ultracentrifugation, electrospray mass spectrometry and measurements of the diffusion constant. Methods that measure the mass or volume under non-native conditions (such as MALDI-TOF mass spectrometry and SDS-PAGE) are generally not useful, since non-native conditions usually cause the complex to dissociate into monomers.

Protein-protein interactions

Proteins are capable of forming very tight complexes. For example, ribonuclease inhibitor binds to ribonuclease A with a roughly 20 fM 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).

The physical interactions holding protein complexes together are, in general, weaker and more polar than those holding the tertiary structure together. Hence, it is sometimes possible to cause a complex to dissociate into folded protein monomers, e.g., by high pressure or high salt concentrations.

External links

[The Macromolecular Structure Database] (MSD) at the European Bioinformatics Institute (EBI) serves a list of the Probabable Quaternary Structure (PQS) for every protein in the Protein Data Bank (PDB).
The Protein Interfaces, Surfaces and Assemblies (Pisa) [server] at the MSD.