Publication details
Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling
| Authors | |
|---|---|
| Year of publication | 2017 |
| Type | Article in Periodical |
| Magazine / Source | Nature Communications |
| MU Faculty or unit | |
| Citation | PETERSEN, J., SC WRIGHT, D. RODRIGUEZ, P. MATRICON, N. LAHAV, A. VROMEN, A. FRIEDLER, J. STROMQVIST, S. WENNMALM, J. CARLSSON and Gunnar SCHULTE. Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling. Nature Communications. London: Nature Publishing Group, 2017, vol. 8, August, p. 1-15. ISSN 2041-1723. Available from: https://dx.doi.org/10.1038/s41467-017-00253-9. |
| Doi | http://dx.doi.org/10.1038/s41467-017-00253-9 |
| Keywords | CROSS-CORRELATION SPECTROSCOPY; MOLECULAR-DYNAMICS SIMULATIONS; A GPCR DIMERS; FRIZZLED 6; ADRENERGIC-RECEPTOR; CONSTANT-PRESSURE; COMPLEX; BINDING; OLIGOMERIZATION; DIMERIZATION |
| Description | G protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors. They can exist and act as dimers, but the requirement of dimers for agonist-induced signal initiation and structural dynamics remains largely unknown. Frizzled 6 (FZD6) is a member of Class F GPCRs, which bind WNT proteins to initiate signaling. Here, we show that FZD6 dimerizes and that the dimer interface of FZD6 is formed by the transmembrane a-helices four and five. Most importantly, we present the agonist-induced dissociation/re-association of a GPCR dimer through the use of live cell imaging techniques. Further analysis of a dimerization-impaired FZD6 mutant indicates that dimer dissociation is an integral part of FZD6 signaling to extracellular signal-regulated kinases1/2. The discovery of agonistdependent dynamics of dimers as an intrinsic process of receptor activation extends our understanding of Class F and other dimerizing GPCRs, offering novel targets for dimerinterfering small molecules. |
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