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TitleStructure and dynamics of the CGRP receptor in apo and peptide-bound forms.
Journal, issue, pagesScience, Year 2021
Publish dateFeb 18, 2021
AuthorsTracy 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 /
PubMed AbstractG protein-coupled receptors (GPCRs) are key regulators of information transmission between cells and organs. Despite this, we have only limited understanding of the behavior of GPCRs in the apo state ...G protein-coupled receptors (GPCRs) are key regulators of information transmission between cells and organs. Despite this, we have only 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 to determine their cryo-EM structures and complemented these with analysis of protein conformational dynamics using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and 3D variance analysis of the cryo-EM data. Together with our previously published structure of the active, Gs-bound, CGRP receptor complex, our work provides important insight into mechanisms of class B1 GPCR activation.
External linksScience / PubMed:33602864
MethodsEM (single particle)
Resolution3.15 - 3.49 Å
Structure data

EMDB-22962, PDB-7knt:
CryoEM structure of the apo-CGRP receptor in a detergent micelle
Method: EM (single particle) / Resolution: 3.15 Å

EMDB-22963, PDB-7knu:
CryoEM structure of the CGRP receptor with bound CGRP peptide in a detergent micelle
Method: EM (single particle) / Resolution: 3.49 Å

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / GPCR / CGRP receptor / apo receptor / MEMBRANE PROTEIN

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