Structural basis of peptide recognition and modulation for neuropeptide FF receptors
文献类型：期刊论文
| 作者 | Li, Xinzhu4,5; Zhang, Heng3; Hu, Wen2; Wu, Kai2; Li, Shuai2; Jin, Sanshan4; Yin, Yuling4; Yuan, Qingning1,2; Xu, H. Eric1,2,3; Pan, Benxun4 |
| 刊名 | CELL REPORTS
 |
| 出版日期 | 2025-09-23 |
| 卷号 | 44期号:9页码:19 |
| ISSN号 | 2639-1856 |
| DOI | 10.1016/j.celrep.2025.116160 |
| 英文摘要 | Neuropeptide FF receptors 1 and 2 (NPFFR1 and NPFFR2) are RF-amide peptide receptors that couple to Gi/o proteins and regulate pain, opioid tolerance, and metabolism. Despite their physiological significance, their ligand selectivity and activation mechanisms remain unclear. Using cryoelectron microscopy, we resolved four NPFFR1 and NPFFR2 structures bound to NPFF or NPVF, revealing conserved C-terminal RF-amide interactions within the orthosteric pocket and N-terminal variations driving subtype specificity. Structural and mutagenesis analyses identified ECL2 and the receptor N terminus as key determinants of NPVF-NPFFR1 and NPFF-NPFFR2 selectivity. Additionally, the structures elucidate the activation mechanism and uncover distinct Gi-coupling features between NPFFR subtypes. These findings provide molecular insights into peptide recognition and receptor activation within the RF-amide family, offering a structural framework for designing selective NPFFR modulators to treat pain, addiction, and metabolic disorders with enhanced specificity and reduced off-target effects. |
| WOS关键词 | PROLACTIN-RELEASING PEPTIDE ; REDUCES FOOD-INTAKE ; NPFF2 RECEPTOR ; ANTAGONIST ; MORPHINE ; IDENTIFICATION ; RFAMIDE ; STIMULATION ; VALIDATION ; MECHANISMS |
| 资助项目 | National Natural Science Foundation of China[32171187] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[32130022] ; Program of Shanghai Academic/Technology Research Leader[22XD1425200] ; Shanghai Oriental Talents Program ; CAS Strategic Priority Research Program[XDB37030103] ; Shanghai Post-doctoral Excellence Program[2023018] ; Shanghai Post-doctoral Excellence Program[2022232] ; Shanghai Sailing Program[23YF1460700] ; Shanghai Sailing Program[22YF1461200] ; China Postdoctoral Science Foundation[2023M731487] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001584152900001 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321600]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Xu, H. Eric; Pan, Benxun; Jiang, Yi |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Natl Res Ctr Translat Med Shanghai, State Key Lab Med Genom, Res Ctr Med Struct Biol,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Adv Electron Microscope Ctr, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 4.Lingang Lab, Shanghai, Peoples R China 5.Shanghai Jiao Tong Univ, Sch Pharmaceut Sci, Shanghai 200240, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xinzhu,Zhang, Heng,Hu, Wen,et al. Structural basis of peptide recognition and modulation for neuropeptide FF receptors[J]. CELL REPORTS,2025,44(9):19. |
| APA | Li, Xinzhu.,Zhang, Heng.,Hu, Wen.,Wu, Kai.,Li, Shuai.,...&Jiang, Yi.(2025).Structural basis of peptide recognition and modulation for neuropeptide FF receptors.CELL REPORTS,44(9),19. |
| MLA | Li, Xinzhu,et al."Structural basis of peptide recognition and modulation for neuropeptide FF receptors".CELL REPORTS 44.9(2025):19. |
入库方式： OAI收割
来源：上海药物研究所
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