Cryo-EM structures of orphan GPR21 signaling complexes
文献类型：期刊论文
| 作者 | Xi Lin6; Bo Chen6; Yiran Wu6; Yingqi Han5; Ao Qi5; Junyan Wang3; Zhao Yang3; Xiaohu Wei6; Tingting Zhao2; Lijie Wu6 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2023 |
| 卷号 | 14期号:1页码:1 |
| ISSN号 | 2041-1723 |
| 英文摘要 | GPR21 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for type 2 diabetes and other metabolic disorders. This receptor shows high basal activity in coupling to multiple G proteins in the absence of any known endogenous agonist or synthetic ligand. Here, we present the structures of ligand-free human GPR21 bound to heterotrimeric miniGs and miniG15 proteins, respectively. We identified an agonist-like motif in extracellular loop 2 (ECL2) that occupies the orthosteric pocket and promotes receptor activation. A side pocket that may be employed as a new ligand binding site was also uncovered. Remarkably, G protein binding is accommodated by a flexible cytoplasmic portion of transmembrane helix 6 (TM6) which adopts little or undetectable outward movement. These findings will enable the design of modulators for GPR21 for understanding its signal transduction and exploring opportunity for deorphanization. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304730]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院 2.南京中医药大学 3.山东大学 4.中国科学院大学 5.中国科学院上海药物研究所 6.上海科技大学 |
| 推荐引用方式 GB/T 7714 | Xi Lin,Bo Chen,Yiran Wu,et al. Cryo-EM structures of orphan GPR21 signaling complexes[J]. NATURE COMMUNICATIONS,2023,14(1):1. |
| APA | Xi Lin.,Bo Chen.,Yiran Wu.,Yingqi Han.,Ao Qi.,...&Fei Xu.(2023).Cryo-EM structures of orphan GPR21 signaling complexes.NATURE COMMUNICATIONS,14(1),1. |
| MLA | Xi Lin,et al."Cryo-EM structures of orphan GPR21 signaling complexes".NATURE COMMUNICATIONS 14.1(2023):1. |
入库方式： OAI收割
来源：上海药物研究所
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