Allosteric control of an asymmetric transduction in a G protein-coupled receptor heterodimer

• DOI: 10.7554/elife.26985
• Publication Date: 2017-08-10T12:00:08Z
• Authors: Junke Liu; Zongyong Zhang; David Moreno-Delgado; James AR Dalton; Xavier Rovira; Ana Trapero; Cyril Goudet; Amadeu Llebaria; Jesús Giraldo; Qilin Yuan; Philippe Rondard; Siluo Huang; Jianfeng Liu; Jean-Philippe Pin
• Keywords: Allosteric modulator

GPCRs play critical roles in cell communication. Although can form heteromers, their role signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs both constitutive homo- and heterodimers. Whereas mGlu2 mGlu4 couple G proteins, protein activation is mediated by heptahelical domain (HD) exclusively mGlu2-4 Such asymmetric transduction results from action of dimeric extracellular domain, an allosteric partially-activated non-functional HD. proteins HD occurs if either occupied a positive modulator or inhibited negative modulator. These data revealed oriented asymmetry mGlu heterodimers that be controlled with modulators. They provide new insight on subunits GPCR dimer.