GPCR interaction as a possible way for allosteric control between receptors

• Published in: Molecular and cellular endocrinology Vol. 486; pp. 89 - 95
• Main Authors: Pin, Jean-Philippe, Kniazeff, Julie, Prézeau, Laurent, Liu, Jiang-Feng, Rondard, Philippe
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.04.2019; Elsevier
• Subjects: Allosteric Regulation; Allostery; Animals; Biochemistry, Molecular Biology; Class C GPCRs; Dimerization; G-protein coupled receptors; GPCR; Humans; Life Sciences; Models, Biological; Neurons and Cognition; plasma membrane; Protein Binding; Protein Domains; Protein Multimerization; Receptors, G-Protein-Coupled - chemistry; Receptors, G-Protein-Coupled - metabolism; Structural Biology; GPCR; Allostery; Class C GPCRs; Dimerization; Allostery; Class C GPCRs; Dimerization; GPCR
• ISSN: 0303-7207; 1872-8057; 1872-8057; 0303-7207
• DOI: 10.1016/j.mce.2019.02.019

For more than twenty years now, GPCR dimers and larger oligomers have been the subject of intense debates. Evidence for a role of such complexes in receptor trafficking to and from the plasma membrane have been provided. However, one main issue is of course to determine whether or not such a phenomenon can be responsible for an allosteric and reciprocal control (allosteric control) of the subunits. Such a possibility would indeed add to the possible ways a cell integrates various signals targeting GPCRs. Among the large GPCR family, the class C receptors that include mGlu and GABAB receptors, represent excellent models to examine such a possibility as they are mandatory dimers. In the present review, we will report on the observed allosteric interaction between the subunits of class C GPCRs, both mGluRs and GABABRs, and on the structural bases of these interactions. We will then discuss these findings for other GPCR types such as the rhodopsin-like class A receptors. We will show that many of the observations made with class C receptors have also been reported with class A receptors, suggesting that the mechanisms involved in the allosteric control between subunits in GPCR dimers may not be unique to class C GPCRs. [Display omitted] •GPCRs can associate into dimers and oligomers.•Class C GPCRs are mandatory dimers, with one subunit only being active at a time.•Class C 7TM domain contact each other via TM6 in the active state only.•TM6 is a key element involved in the negative allostery between the 7TM domains.•Class A GPCR dimers share many of the features of class C dimers.