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| Title | Structure and dynamics of the CGRP receptor in apo and peptide-bound forms. |
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| Journal, issue, pages | Science, Vol. 372, Issue 6538, Year 2021 |
| Publish date | Apr 9, 2021 |
 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 /    |
| PubMed 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. |
 External links | Science / PubMed:33602864 |
| Methods | EM (single particle) |
| Resolution | 3.15 - 3.49 Å |
| Structure data | EMDB-22962, PDB-7knt: EMDB-22963, PDB-7knu: |
| Source |
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 Keywords |  SIGNALING PROTEIN / GPCR / CGRP receptor / apo receptor / MEMBRANE PROTEIN |
