Glutamate binding triggers monomerization of unliganded mGluR2 dimers.

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 Forster Resonance Energy Transfer (FRET) based assay 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 an unstructured loop, mGluR2 neither undergoes conformational change nor monomerizes upon binding to glutamate.

journal_name

Arch Biochem Biophys

authors

Singh DR,Pandey K,Mishra AK,Pandey P,Vivcharuk V

doi

10.1016/j.abb.2020.108632

subject

Has Abstract

pub_date

2021-01-15 00:00:00

pages

108632

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(20)30641-X

journal_volume

697

pub_type

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