Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

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


Khoshouei,  Maryam
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

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.

Cite as: https://hdl.handle.net/21.11116/0000-0005-F9DD-A
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.