Glutamate binding triggers monomerization of unliganded mGluR2 dimers.

Glutamate binding triggers monomerization of unliganded mGluR2 dimers.
Arch Biochem Biophys. 2020 Oct 16;:108632
Authors: Singh DR, Pandey K, Mishra AK, Pandey P, Vivcharuk V
Abstract
The Metabotropic glutamate receptor 2 (mGluR2) is involved in several neurological and psychiatric disorders and is an attractive drug target. It is believed to form a strict dimer and the dimeric assembly is necessary for glutamate induced activation. Although, many studies have focused on glutamate induced conformational changes, the dimerization propensity of mGluR2 with and without glutamate has never been investigated. Also, the role of the unstructured loop in dimerization of mGluR2 is not clear. Here, using Förster Resonance Energy Transfer (FRET) based assays in live cells we show that mGluR2 does not form a "strict dimer" rather it exists in a dynamic monomer-dimer equilibrium. The unstructured loop moderately destabilizes the dimers. Furthermore, binding of glutamate to mGluR2 induces conformational change that promotes monomerization of mGluR2. In the absence of unstructured loop, mGluR2 neither undergoes conformational change nor monomerizes upon binding to glutamate.
PMID: 33075300 [PubMed - as supplied by publisher]

Source: Archives of Biochemistry and Biophysics - October 16, 2020 Category: Biochemistry Authors: Singh DR, Pandey K, Mishra AK, Pandey P, Vivcharuk V Tags: Arch Biochem Biophys Source Type: research