XFEL structures of the human MT₂ melatonin receptor reveal the basis of subtype selectivity.

ABSTRACT: The human MT₁ and MT₂ melatonin receptors^1,2 are G-protein-coupled receptors (GPCRs) that help to regulate circadian rhythm and sleep patterns³. Drug development efforts have targeted both receptors for the treatment of insomnia, circadian rhythm and mood disorders, and cancer³, and MT₂ has also been implicated in type 2 diabetes^4,5. Here we report X-ray free electron laser (XFEL) structures of the human MT₂ receptor in complex with the agonists 2-phenylmelatonin (2-PMT) and ramelteon⁶ at resolutions of 2.8 Å and 3.3 Å, respectively, along with two structures of function-related mutants: H208^5.46A (superscripts represent the Ballesteros-Weinstein residue numbering nomenclature

SUBMITTER: Johansson LC 

PROVIDER: S-EPMC6589158 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature