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  Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation

Liang, Y.-L., Belousoff, M. J., Zhao, P., Koole, C., Fletcher, M. M., Truong, T. T., et al. (2020). Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation. MOLECULAR CELL, 77(3), 656-668. doi:10.1016/j.molcel.2020.01.012.

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Genre: Journal Article

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 Creators:
Liang, Yi-Lynn1, Author
Belousoff, Matthew J.1, Author
Zhao, Peishen1, Author
Koole, Cassandra1, Author
Fletcher, Madeleine M.1, Author
Truong, Tin T.1, Author
Julita, Villy1, Author
Christopoulos, George1, Author
Xu, H. Eric1, Author
Zhang, Yan1, Author
Khoshouei, Maryam2, Author              
Christopoulos, Arthur1, Author
Danev, Radostin1, Author
Sexton, Patrick M.1, Author
Wootten, Denise1, Author
Affiliations:
1external, ou_persistent22              
2Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              

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Free keywords: CRYO-EM STRUCTURE; CORTICOTROPIN-RELEASING-FACTOR; GLP-1 RECEPTOR; DETERMINANTS; RECOGNITION; DYNAMICS; COMPLEX; SURFACE
 Abstract: Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gsbound 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.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: 18
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: MOLECULAR CELL
Source Genre: Journal
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Publ. Info: 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 77 (3) Sequence Number: - Start / End Page: 656 - 668 Identifier: ISSN: 1097-2765