Rational design of a Kappa opioid receptor peptide agonist with attenuated β-arrestin signaling
C-Met NMR analyses further reveal beta01 stabilizes a unique KOR conformation with an expanded intracellular cavity that disfavors β-arrestin binding. This work establishes a rational structure-based framework for designing safer and more effective GPCR-targeted therapeutics.
Authors
- Z Xu
- Gaoming Wang
- 刘英斌
- Youwen Zhuang (ORCID: https://orcid.org/0000-0002-1380-8047)
- Qingjun Zhu (ORCID: https://orcid.org/0000-0001-6473-2153)
- Xinheng He
- Youwei Xu
- H Eric Xu
- Jun Liang
- Changlin Tian (ORCID: https://orcid.org/0000-0001-9315-900X)
- Pan Shi
- Pei Lv
- Qingning Yuan
- Yong Zheng
- Li Zhou
- Huanhuan Zhang
- Wen Hu
- Kai Wu
- Fan Yang
Institutions
- University of Science and Technology of China (CN)
- Nanjing University of Chinese Medicine (CN)
- Shanghai Jiao Tong University (CN)
- Anhui University of Science and Technology (CN)
- Chinese Academy of Sciences (CN)
- Renji Hospital (CN)
- Hefei Institutes of Physical Science (CN)
- Suzhou University of Science and Technology (CN)
- High Magnetic Field Laboratory (CN)
- Shanghai Institute of Materia Medica (CN)
- Beijing Academy of Science and Technology (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1038/s41467-026-71455-3
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China