Allosteric control of an asymmetric transduction in a G protein-coupled receptor heterodimer
Liu, Junke (University of Science and Technology, Wuhan, China)
Zhang, Zongyong (University of Science and Technology, Wuhan, China)
Moreno-Delgado, David (Université de Montpellier, France)
Dalton, James A. R (Universitat Autònoma de Barcelona. Institut de Neurociències)
Rovira, Xavier (Université de Montpellier, France)
Trapero, Ana (Institut de Química Avançada de Catalunya)
Goudet, Cyril (Université de Montpellier, France)
Llebaria, Amadeu (Institut de Química Avançada de Catalunya)
Giraldo, Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Yuan, Qilin (University of Science and Technology, Wuhan, China)
Rondard, Philippe (Université de Montpellier, France)
Huang, Siluo (University of Science and Technology, Wuhan, China)
Liu, Jianfeng (University of Science and Technology, Wuhan, China)
Pin, Jean-Philippe (Université de Montpellier, France)
Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública

Date:	2017
Abstract:	GPCRs play critical roles in cell communication. Although GPCRs can form heteromers, their role in signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs can form both constitutive homo- and heterodimers. Whereas both mGlu2 and mGlu4 couple to G proteins, G protein activation is mediated by mGlu4 heptahelical domain (HD) exclusively in mGlu2-4 heterodimers. Such asymmetric transduction results from the action of both the dimeric extracellular domain, and an allosteric activation by the partially-activated non-functional mGlu2 HD. G proteins activation by mGlu2 HD occurs if either the mGlu2 HD is occupied by a positive allosteric modulator or if mGlu4 HD is inhibited by a negative modulator. These data revealed an oriented asymmetry in mGlu heterodimers that can be controlled with allosteric modulators. They provide new insight on the allosteric interaction between subunits in a GPCR dimer.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	eLife, Vol. 6 (august 2017) , ISSN 2050-084X

DOI: 10.7554/eLife.26985
PMID: 28829739

19 p, 1.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles