التفاصيل البيبلوغرافية
| العنوان: |
Structural insights into the human niacin receptor HCA2-Gi signalling complex. |
| المؤلفون: |
Yang, Yang, Kang, Hye Jin, Gao, Ruogu, Wang, Jingjing, Han, Gye Won, DiBerto, Jeffrey F., Wu, Lijie, Tong, Jiahui, Qu, Lu, Wu, Yiran, Pileski, Ryan, Li, Xuemei, Zhang, Xuejun Cai, Zhao, Suwen, Kenakin, Terry, Wang, Quan, Stevens, Raymond C., Peng, Wei, Roth, Bryan L., Rao, Zihe |
| المصدر: |
Nature Communications; 3/27/2023, Vol. 14 Issue 1, p1-11, 11p |
| مصطلحات موضوعية: |
NIACIN, NICOTINAMIDE, NICOTINIC receptors, LIGAND binding (Biochemistry), CRYSTAL structure |
| مستخلص: |
The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-Gi signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors. Hydroxyl-carboxylic acid receptor 2 (HCA2) functions as a high-affinity receptor for nicotinic acid (vitamin B3). Here, authors report the cryo-EM structure of the HCA2-Gi complex with the agonist MK-6892 and inactive state crystal structures of mutation stabilized HCA2, to describe the mechanism of HCA2 signaling. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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