| Title |
Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1 |
| Description |
Here we report the G protein bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the frst transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis defcient ADGRF1, supporting a cleavage independent manner of receptor activation. The stalk induced activation is facilitated by a cascade of inter helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. |
| Organism |
Homo sapiens |
| Data Type |
Protein 3D Structure Data |
| Data Accessibility |
Controlled-access |
| BioProject |
PRJCA016824 |
| Release Date |
2024-12-31 |
| Submitter |
wenru zhang (wrzhang@simm.ac.cn) |
| Organization |
Shanghai nstitute of Material Medica |
| Submission Date |
2023-05-08 |