Folded proteins generally speaking do not function in isolation, instead they form part of complexes with other biological molecules. These complexes are composed of many molecules which act in symphony to facilitate biological reactions.
The quaternary structure of a protein is the structure that a protein forms with other molecules as part of its final functional form (Figure 1). There are many types of quaternary structure, which differ in which molecules the protein interacts with, and how long the interactions take place.
Figure 1: The quaternary structure of the cJun-cFos AP-1 transcription factor bound to DNA (PDB ID: 1FOS). This quaternary structure includes protein-protein interactions in the dimerization of the cJun (yellow) and cFos (red) proteins to form the AP-1 transcription factor, and protein-ligand interactions in the binding between the AP-1 and the DNA (blue).
Interactions between proteins are called protein-protein interactions. whereas those with non-protein molecules are called protein-ligand interactions. Protein quaternary structure may include both types of these interactions. Haemoglobin, the oxygen carrying protein found in the blood forms protein-protein interactions with other haemoglobin molecules, and also protein-ligand interactions with the haem molecule that carries oxygen.
Interactions can be characterized as strong, long lasting interactions, while others are short lived transient interactions. Proteins like cell membrane proteins remain in the cell membrane, and thus form strong interaction with the phospholipids in that membrane (though not necessarily the same identical phospholipid molecules). The native state of a membrane protein is therefore bound to phospholipid molecules. Haemoglobin is also in strong interactions with the other proteins and ligands that form part of its complex. Often these complexes are easy to derive structures of, as they often form spontaneously, and are often stable during the processes used to derive protein structures.
By contrast, other protein interactions are transient. They take place for short amounts of time and happen in the course of specific reactions. Cell membrane proteins are often receptors for specific molecules. They will interact with the molecule in a way that induces a response inside the cell, but not necessarily bind to the molecule permanently. These types of short lived interactions are more difficult to derive, due to their short lived nature. However techniques like confocal microscopy and single molecule imaging may be able to detect that these interactions are taking place.
Protein structures, from primary to quaternary are essential for the protein function. Without the correct structure being formed, protein function does not occur, and in fact unintended functions may occur that can cause disease.