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-Structure paper
Title | Structural basis of CD97 activation and G-protein coupling. |
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Journal, issue, pages | Cell Chem Biol, Vol. 30, Issue 11, Page 1343-11353.e5, Year 2023 |
Publish date | Nov 16, 2023 |
Authors | Na Wang / Yu Qian / Ruixue Xia / Xinyan Zhu / Yangjie Xiong / Anqi Zhang / Changyou Guo / Yuanzheng He / |
PubMed Abstract | CD97 (ADGRE5) is an adhesion G protein-coupled receptor (aGPCR) which plays crucial roles in immune system and cancer. However, the mechanism of CD97 activation and the determinant of G coupling ...CD97 (ADGRE5) is an adhesion G protein-coupled receptor (aGPCR) which plays crucial roles in immune system and cancer. However, the mechanism of CD97 activation and the determinant of G coupling selectivity remain unknown. Here, we present the cryo-electron microscopy structures of human CD97 in complex with G, G, and G. Our structures reveal the stalk peptide recognition mode of CD97, adding missing information of the current tethered-peptide activation model of aGPCRs. For instance, a revised "FXφφφ" motif and a framework of conserved aromatic residues in the ligand-binding pocket. Importantly, structural comparisons of G, G, and G engagements of CD97 reveal key determinants of G coupling selectivity, where a deep insertion of the α helix 5 and a closer contact with the transmembrane helix 6, 5, and 3 dictate coupling preferences. Taken together, our structural study of CD97 provides a framework for understanding CD97 signaling and the G coupling selectivity. |
External links | Cell Chem Biol / PubMed:37673067 |
Methods | EM (single particle) |
Resolution | 2.89 - 3.1 Å |
Structure data | EMDB-33747: CD97/miniG13 complex EMDB-33753: CD97/Gq complex EMDB-33755, PDB-7ydp: |
Source |
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Keywords | MEMBRANE PROTEIN / GPCR-G-protein complex |