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DOI	10.1073/pnas.2019497118
	Nucleic acid ligands act as a PAM and agonist depending on the intrinsic ligand binding state of P2RY2
	Takahashi M.; Amano R.; Ozawa M.; Martinez A.; Akita K.; Nakamura Y.
发表日期	2021
ISSN	00278424
卷号	118 期号:18
英文摘要	G protein-coupled receptors (GPCRs) play diverse roles in physiological processes, and hence the ligands to modulate GPCRs have served as important molecules in biological and pharmacological approaches. However, the exploration of novel ligands for GPCR still remains an arduous challenge. In this study, we report a method for the discovery of nucleic acid ligands against GPCRs by an advanced RNA aptamer screening technology that employs a virus-like particle (VLP), exposing the GPCR of interest. An array of biochemical analyses coupled with a cell-based assay revealed that one of the aptamers raised against purinergic receptor P2Y2 (P2RY2), a GPCR, exhibits an activation potency to unliganded receptor and prohibits a further receptor activation by endogenous ligand, behaving like a partial agonist. However, the aptamer enhances the activity of intrinsic ligand-binding P2RY2, thereby acting as a positive allosteric modulator (PAM) to liganded receptor. Our findings demonstrate that the nucleic acid aptamer conditionally exerts PAM and agonist effects on GPCRs, depending on their intrinsic ligand binding state. These results indicate the validity of our VLP-based aptamer screening targeting GPCR and reemphasize the great potential of nucleic acid ligands for exploring the GPCR activation mechanism and therapeutic applications. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	GPCR; Nucleic acid aptamer; P2RY2; PAM agonist
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179700
作者单位	Project Division of RNA Medical Science, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; RIBOMIC Inc., Tokyo, 108-0071, Japan
推荐引用方式 GB/T 7714	Takahashi M.,Amano R.,Ozawa M.,et al. Nucleic acid ligands act as a PAM and agonist depending on the intrinsic ligand binding state of P2RY2[J],2021,118(18).
APA	Takahashi M.,Amano R.,Ozawa M.,Martinez A.,Akita K.,&Nakamura Y..(2021).Nucleic acid ligands act as a PAM and agonist depending on the intrinsic ligand binding state of P2RY2.Proceedings of the National Academy of Sciences of the United States of America,118(18).
MLA	Takahashi M.,et al."Nucleic acid ligands act as a PAM and agonist depending on the intrinsic ligand binding state of P2RY2".Proceedings of the National Academy of Sciences of the United States of America 118.18(2021).