National Health and Medical Research Council (NHMRC, Australia)
1061044
Australia
National Health and Medical Research Council (NHMRC, Australia)
1065410
Australia
National Health and Medical Research Council (NHMRC, Australia)
1126857
Australia
National Health and Medical Research Council (NHMRC, Australia)
1055134
Australia
Citation
Journal: Science / Year: 2021 Title: Structure and dynamics of the CGRP receptor in apo and peptide-bound forms. Authors: Tracy M Josephs / Matthew J Belousoff / Yi-Lynn Liang / Sarah J Piper / Jianjun Cao / Daniel J Garama / Katie Leach / Karen J Gregory / Arthur Christopoulos / Debbie L Hay / Radostin Danev / ...Authors: Tracy M Josephs / Matthew J Belousoff / Yi-Lynn Liang / Sarah J Piper / Jianjun Cao / Daniel J Garama / Katie Leach / Karen J Gregory / Arthur Christopoulos / Debbie L Hay / Radostin Danev / Denise Wootten / Patrick M Sexton / Abstract: 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 ...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.
History
Deposition
Nov 6, 2020
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Header (metadata) release
Feb 24, 2021
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Map release
Feb 24, 2021
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Update
Apr 21, 2021
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Current status
Apr 21, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
EMPIAR-10671 (Title: CryoEM structure of the CGRP receptor with bound CGRP peptide in a detergent micelle Data size: 1.6 TB Data #1: Non-gain-normalized LZW-TIFF compressed movies of CGRPR-CGRP in a detergent micelle [micrographs - multiframe])
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