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Updated: Jul 17, 2025

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
Structural basis of CD97 activation and G-protein coupling
Na Wang1, Yu Qian1, Ruixue Xia1
1Laboratory of Receptor Structure and Signaling, HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
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 G13 coupling selectivity remain unknown. Here, we present the cryo-electron microscopy structures of human CD97 in complex with G13, Gq, and Gs. 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 G13, Gq, and Gs engagements of CD97 reveal key determinants of G13 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 G13 coupling selectivity.
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