Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor
文献类型：期刊论文
| 作者 | Ma Shanshan2; Chen Yan2; Dai Antao1; Yin Wanchao2; Guo Jia2; Yang Dehua2 ; Zhou Fulai2; Jiang Yi2; Wang Mingwei2; Eric Xu H2
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| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2021 |
| 卷号 | 31期号:10页码:1061 |
| 关键词 | Cryoelectron microscopy Single-molecule biophysics |
| ISSN号 | 1001-0602 |
| 英文摘要 | Melanocortins are peptide hormones critical for the regulation of stress response, energy homeostasis, inflammation, and skin pigmentation. Their functions are mediated by five G protein-coupled receptors (MC1R-MC5R), predominately through the stimulatory G protein (Gs). MCI R, the founding member of melanocortin receptors, is mainly expressed in melanocytes and is involved in melanogenesis. Dysfunction of MC1R is associated with the development of melanoma and skin cancer. Here we present three cryo-electron microscopy structures of the MC1R-Gs complexes bound to endogenous hormone a-MSH, a marketed drug afamelanotide, and a synthetic agonist SHU9119. These structures reveal the orthosteric binding pocket for the conserved HFRW motif among melanocortins and the crucial role of calcium ion in ligand binding. They also demonstrate the basis of differential activities among different ligands. In addition, unexpected interactions between MC1R and the Gβ subunit were discovered from these structures. Together, our results elucidate a conserved mechanism of calcium-mediated ligand recognition, a specific mode of G protein coupling, and a universal activation pathway of melanocortin receptors. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304803]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.The National Center for Drug Screening,Shanghai Institute of Materia Medica,Chinese Academy of Sciences 2.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Ma Shanshan,Chen Yan,Dai Antao,et al. Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor[J]. CELL RESEARCH,2021,31(10):1061. |
| APA | Ma Shanshan.,Chen Yan.,Dai Antao.,Yin Wanchao.,Guo Jia.,...&Eric Xu H.(2021).Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor.CELL RESEARCH,31(10),1061. |
| MLA | Ma Shanshan,et al."Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor".CELL RESEARCH 31.10(2021):1061. |
入库方式： OAI收割
来源：上海药物研究所
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