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Publication Abstract from PubMed

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.

Structure and dynamics of the CGRP receptor in apo and peptide-bound forms.,Josephs TM, Belousoff MJ, Liang YL, Piper SJ, Cao J, Garama DJ, Leach K, Gregory KJ, Christopoulos A, Hay DL, Danev R, Wootten D, Sexton PM Science. 2021 Apr 9;372(6538):eabf7258. doi: 10.1126/science.abf7258. Epub 2021 , Feb 18. PMID:33602864^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.