Structural mechanisms for self-activation of protease-activated receptor 4 by tethered ligand
signaling is uniquely modulated by shallow engagement of the wavy hook, which disrupts its interaction with the DRY motif. Molecular docking demonstrates that the selective agonist PAR4-AP enhances activation through additional hydrophobic contacts and a stabilizing salt bridge, revealing the determinants of subtype selectivity. These findings provide mechanistic insights into PAR4 signaling, laying a foundation for the discovery of PAR4-targeted antithrombotic drugs.
Authors
- Weiqiang Lü (ORCID: https://orcid.org/0000-0003-1349-6597)
- Zhefan Yu (ORCID: https://orcid.org/0000-0001-5179-6131)
- Xiaolei Chai
- Y Zhang
- Qiansen Zhang (ORCID: https://orcid.org/0000-0002-8608-3067)
- Haitao Zhang (ORCID: https://orcid.org/0000-0003-4879-2951)
- Anqi Chen (ORCID: https://orcid.org/0000-0002-9480-9059)
- Zhikang Xu
- Jiacheng He
- Zihan Zhou
- Mingyao Liu
- Jian Zhang
Institutions
- Hainan Normal University (CN)
- Shanghai Jiao Tong University (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- East China Normal University (CN)
- Zhejiang University (CN)
- Hainan Medical University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-06-30
- DOI
- https://doi.org/10.1016/j.celrep.2026.117632
- Primary Topic
- Blood Coagulation and Thrombosis Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- National Major Science and Technology Projects of China
- Natural Science Foundation of Zhejiang Province