National Health and Medical Research Council (NHMRC, Australia)
1120919
オーストラリア
National Health and Medical Research Council (NHMRC, Australia)
1150083
オーストラリア
National Health and Medical Research Council (NHMRC, Australia)
1159006
オーストラリア
Japan Science and Technology
18069571
日本
Japan Society for the Promotion of Science (JSPS)
18H06043
日本
引用
ジャーナル: Mol Cell / 年: 2020 タイトル: Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation. 著者: Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / ...著者: Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / Arthur Christopoulos / Radostin Danev / Patrick M Sexton / Denise Wootten / 要旨: Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, ...Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, PAC1 receptor, and corticotropin-releasing factor (CRF), (CRF1) receptor. Together with recently solved structures, these provide coverage of the major class B GPCR subfamilies. Diverse orientations of the extracellular domain to the receptor core in different receptors are at least partially dependent on evolutionary conservation in the structure and nature of peptide interactions. Differences in peptide interactions to the receptor core also influence the interlinked TM2-TM1-TM6/ECL3/TM7 domain, and this is likely important in their diverse signaling. However, common conformational reorganization of ECL2, linked to reorganization of ICL2, modulates G protein contacts. Comparison between receptors reveals ICL2 as a key domain forming dynamic G protein interactions in a receptor- and ligand-specific manner. This work advances our understanding of class B GPCR activation and Gs coupling.
EMPIAR-10361 (タイトル: Cryo-EM of CRF1 receptor bound to CRF and Gs protein Data size: 2.6 TB Data #1: Unaligned multi-frame gain-normalized movies in LZW compressed TIFF format [micrographs - multiframe])