Structure and dynamics of the CGRP receptor in apo and peptide-bound forms.
Tracy M JosephsMatthew J BelousoffYi-Lynn LiangSarah J PiperJianjun CaoDaniel J GaramaKatie LeachKaren J GregoryArthur ChristopoulosDebbie L HayRadostin DanevDenise WoottenPatrick M SextonPublished in: Science (New York, N.Y.) (2021)
G protein-coupled receptors (GPCRs) are key regulators of information transmission between cells and organs. Despite this, we have only a limited understanding of the behavior of GPCRs in the apo state and the conformational changes upon agonist binding that lead to G protein recruitment and activation. We expressed and purified unmodified apo and peptide-bound calcitonin gene-related peptide (CGRP) receptors from insect cells to determine their cryo-electron microscopy (cryo-EM) structures, and we complemented these with analysis of protein conformational dynamics using hydrogen-deuterium exchange mass spectrometry and three-dimensional variance analysis of the cryo-EM data. Together with our previously published structure of the active, Gs-bound CGRP receptor complex, our work provides insight into the mechanisms of class B1 GPCR activation.
Keyphrases
- induced apoptosis
- electron microscopy
- mass spectrometry
- high resolution
- cell cycle arrest
- molecular dynamics
- molecular dynamics simulations
- binding protein
- single molecule
- randomized controlled trial
- transcription factor
- cell death
- dna methylation
- gene expression
- signaling pathway
- big data
- machine learning
- health information
- dna binding
- artificial intelligence
- pi k akt
- high performance liquid chromatography
- data analysis
- simultaneous determination