GPCR-Oligomer

A GPCR oligomer is a designated as an oligomer association or complex are held together of several G- protein -coupled receptors, which have a direct contact with each other and by atomic bonds or intermolecular forces. Receptors within the association called protomers, while unrelated receptors are referred to as monomers. Receptor homomers composed of the same, heteromers of dissimilar protomers. Receptors associations, which as such, but not in the form of their Stammmonomere natively capable of transmission of stimuli are referred to as constitutive receptors. Receptors, which are only indirectly connected to each other, are not referred to as oligomers. The functional effect of a ligand binding to be transmitted from one protomer on one or more other protomers is called crosstalk. The specific nature of the functional interaction of ligands, which results from the binding to two or more protomers a complex, expressed as cooperativity.

The existence of receptor oligomers is a general phenomenon, which has removed the long time dominant paradigmatic conception of the function of receptors as pure monomers and their discovery has far-reaching consequences for the understanding of neurobiological diseases and for the development of drugs. Receptor oligomers and their function in the interactome are researched according to their importance intensive.

The oligomerization is not limited to G protein- coupled receptors, but is also observed in other target proteins, such as plasmalemmal transporters and ion channels. A cross-group functional interaction is possible.

Discovery history

For a long time it was assumed, receptors, effects transmitted exclusively in their functional prototypes - as monomers. The first indication of the existence of GPCR oligomers goes back to the year 1975. Lefkowitz and co-workers had observed on beta- adrenoceptors a behavior that is known as negative cooperativity and is based on the existence of receptor dimers or oligomers. At the beginning of the 1980s, it was hypothesized, receptors could be larger associations, called mosaics form, or two receptors may interact directly with each other. Mass determinations of beta- adrenoceptors (1982) and muscarinic (1983 ) showed that may exist in homodimeric or tetrameric forms of the receptors. 1991 phenomena have been observed, which can be interpreted as crosstalk, and so pointing to a heteromer receptor expression. The study focused on adenosine A2A and dopamine D2 receptors. Maggio and co-workers showed in 1993 the ability of two G- protein -coupled receptors to heteromerize by they used chimeras of muscarinic M3 receptors and α2C -adrenoceptors.

In 2005, evidence was provided that Rezeptoroligomeren plays functional role in the living organism. The crystal structure of CXCR4 dimer was published in 2010.

Properties of the oligomers

Effect of oligomerization

GPCR oligomers exist higher order of dimers, trimers, tetramers or associations. The oligomers are to be regarded as entities that have properties that differ from those of the monomers and more or less in many ways. The functional character of a receptor depends on its tertiary or quartärstrukturellen shape. Receptors to touch on a larger area or at sensitive places, then act forces that change the shape as well as the internal mobility of the reorganized protomers; in short, protomers act as allosteric modulators one another. This has consequences for:

• The supply of cell surface receptors with
• The ligand binding to different binding sites
• The G- protein coupling
• The innerzelluären navigation (see signal transduction)
• Modifying the Desensibilisierungsprofile
• The tendency to endocytosis and internalization
• Postendozytotische the fate of the receptors

Examples

It is currently unclear whether all Rezeptoroligomere have a functional role in signal transmission.