Structure and dynamics of the CGRP receptor in apo and peptide-bound forms

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.

Source: ScienceNOW - April 8, 2021 Category: Science Authors: Josephs, T. M., Belousoff, M. J., Liang, Y.-L., Piper, S. J., Cao, J., Garama, D. J., Leach, K., Gregory, K. J., Christopoulos, A., Hay, D. L., Danev, R., Wootten, D., Sexton, P. M. Tags: Biochemistry, Cell Biology, Online Only r-articles Source Type: news