Asset Details
Do you wish to reserve the book?
Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer
Do you wish to request the book?
Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer
2015
Overview
Disulfide trapping and FRET studies define an agonist-induced conformational change in mGlu2 from inactive symmetric dimers with an interface at transmembrane domains (TMs) 4 and 5 to an active state with TM6s serving as the dimer interface.
G protein–coupled receptors (GPCRs) are major players in cell communication. Although they form functional monomers, increasing evidence indicates that GPCR dimerization has a critical role in cooperative phenomena that are important for cell signal integration. However, the structural bases of these phenomena remain elusive. Here, using well-characterized receptor dimers, the metabotropic glutamate receptors (mGluRs), we show that structural changes at the dimer interface are linked to receptor activation. We demonstrate that the main dimer interface is formed by transmembrane α helix 4 (TM4) and TM5 in the inactive state and by TM6 in the active state. This major change in the dimer interface is required for receptor activity because locking the TM4-TM5 interface prevents activation by agonist, whereas locking the TM6 interface leads to a constitutively active receptor. These data provide important information on the activation mechanism of mGluRs and improve our understanding of the structural basis of the negative cooperativity observed in these GPCR dimers.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 631/378
/ 631/45
/ 82
/ 9/10
/ 96
/ 96/33
/ 96/34
/ Animals
/ Cells
/ Humans
/ Ligands
/ Rats
/ Receptor, Metabotropic Glutamate 5 - agonists
/ Receptor, Metabotropic Glutamate 5 - chemistry
/ Receptor, Metabotropic Glutamate 5 - genetics
/ Receptors, GABA-B - chemistry
/ Receptors, GABA-B - genetics
/ Receptors, GABA-B - metabolism
/ Receptors, Metabotropic Glutamate - agonists
/ Receptors, Metabotropic Glutamate - chemistry
