Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure and Dynamics of Adrenomedullin Receptors AM and AM Reveal Key Mechanisms in the Control of Receptor Phenotype by Receptor Activity-Modifying Proteins.
Journal, issue, pages	ACS Pharmacol Transl Sci, Vol. 3, Issue 2, Page 263-284, Year 2020
Publish date	Apr 10, 2020
Authors	Yi-Lynn Liang / Matthew J Belousoff / Madeleine M Fletcher / Xin Zhang / Maryam Khoshouei / Giuseppe Deganutti / Cassandra Koole / Sebastian G B Furness / Laurence J Miller / Debbie L Hay / Arthur Christopoulos / Christopher A Reynolds / Radostin Danev / Denise Wootten / Patrick M Sexton /
PubMed Abstract	Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) receptors are critically important for metabolism, vascular tone, and inflammatory response. AM receptors are also required for normal ...Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) receptors are critically important for metabolism, vascular tone, and inflammatory response. AM receptors are also required for normal lymphatic and blood vascular development and angiogenesis. They play a pivotal role in embryo implantation and fertility and can provide protection against hypoxic and oxidative stress. CGRP and AM receptors are heterodimers of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) (CGRPR), as well as RAMP2 or RAMP3 (AMR and AMR, respectively). However, the mechanistic basis for RAMP modulation of CLR phenotype is unclear. In this study, we report the cryo-EM structure of the AMR in complex with AM and Gs at a global resolution of 3.0 Å, and structures of the AMR in complex with either AM or intermedin/adrenomedullin 2 (AM2) and Gs at 2.4 and 2.3 Å, respectively. The structures reveal distinctions in the primary orientation of the extracellular domains (ECDs) relative to the receptor core and distinct positioning of extracellular loop 3 (ECL3) that are receptor-dependent. Analysis of dynamic data present in the cryo-EM micrographs revealed additional distinctions in the extent of mobility of the ECDs. Chimeric exchange of the linker region of the RAMPs connecting the TM helix and the ECD supports a role for this segment in controlling receptor phenotype. Moreover, a subset of the motions of the ECD appeared coordinated with motions of the G protein relative to the receptor core, suggesting that receptor ECD dynamics could influence G protein interactions. This work provides fundamental advances in our understanding of GPCR function and how this can be allosterically modulated by accessory proteins.
External links	ACS Pharmacol Transl Sci / PubMed:32296767 / PubMed Central
Methods	EM (single particle)
Resolution	2.3 - 3.0 Å
Structure data	20883 6uun EMDB-20883, PDB-6uun: CryoEM Structure of the active Adrenomedullin 1 receptor G protein complex with adrenomedullin peptide Method: EM (single particle) / Resolution: 3.0 Å 20901 6uus EMDB-20901, PDB-6uus: CryoEM Structure of the active Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide Method: EM (single particle) / Resolution: 2.4 Å 20906 6uva EMDB-20906, PDB-6uva: CryoEM Structure of the active Adrenomedullin 2 receptor G protein complex with adrenomedullin 2 peptide Method: EM (single particle) / Resolution: 2.3 Å
Source	homo sapiens (human) lama glama (llama)
Keywords	MEMBRANE PROTEIN / GPCR / adrenomedullin receptor complex / adrenomedullin 2 receptor complex