Importance of the second extracellular loop for melatonin MT₁ receptor function and absence of melatonin binding in GPR50.

ABSTRACT:

Background and purpose

Recent crystal structures of GPCRs have emphasized the previously unappreciated role of the second extracellular (E2) loop in ligand binding and gating and receptor activation. Here, we have assessed the role of the E2 loop in the activation of the melatonin MT₁ receptor and in the inactivation of the closely related orphan receptor GPR50.

Experimental approach

Chimeric MT₁ -GPR50 receptors were generated and functionally analysed in terms of 2-[¹²⁵ I]iodomelatonin binding, G_i /cAMP signalling and β-arrestin2 recruitment. We also used computational molecular dynamics (MD) simulations.

Key results

MD simulations of 300 ns revealed (i) the tight hairpin structure of the E2 loop of the MT₁ rece

SUBMITTER: Clement N 

PROVIDER: S-EPMC6057912 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature