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DOI	10.1016/j.scib.2020.12.006
	The structural basis for glycerol permeation by human AQP7
	Zhang L.; Yao D.; Xia Y.; Zhou F.; Zhang Q.; Wang Q.; Qin A.; Zhao J.; Li D.; Li Y.; Zhou L.; Cao Y.
发表日期	2021
ISSN	20959273
起始页码	1550
结束页码	1558
卷号	66 期号:15
英文摘要	Human glycerol channel aquaporin 7 (AQP7) conducts glycerol release from adipocyte and enters the cells in pancreatic islets, muscles, and kidney tubules, and thus regulates glycerol metabolism in those tissues. Compared with other human aquaglyceroporins, AQP7 shows a less conserved “NPA” motif in the center cavity and a pair of aromatic residues at Ar/R selectivity filter. To understand the structural basis for the glycerol conductance, we crystallized the human AQP7 and determined the structure at 3.7 Å. A substrate binding pocket was found near the Ar/R filter where a glycerol molecule is bound and stabilized by R229. Glycerol uptake assay on human AQP7 as well as AQP3 and AQP10 demonstrated strong glycerol transportation activities at the physiological condition. The human AQP7 structure, in combination with the molecular dynamics simulation thereon, reveals a fully closed conformation with its permeation pathway strictly confined by the Ar/R filter at the exoplasmic side and the gate at the cytoplasmic side, and the binding of glycerol at the Ar/R filter plays a critical role in controlling the glycerol flux by driving the dislocation of the residues at narrowest parts of glycerol pathway in AQP7. © 2021 Science China Press
关键词	Aquaglyceroporins Glycerol metabolism Glycerol transportation Structural biology
英文关键词	Cell proliferation; Molecular dynamics; Aromatic residues; Glycerol channels; Molecular dynamics simulations; Pancreatic islet; Physiological condition; Selectivity filter; Structural basis; Substrate binding; Glycerol
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207669
作者单位	CAS Center for Excellence on Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 201210, China; Institute of Precision Medicine, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China; iHuman Institute, ShanghaiTech University, Shanghai, 201210, China; Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 200433, China
推荐引用方式 GB/T 7714	Zhang L.,Yao D.,Xia Y.,et al. The structural basis for glycerol permeation by human AQP7[J],2021,66(15).
APA	Zhang L..,Yao D..,Xia Y..,Zhou F..,Zhang Q..,...&Cao Y..(2021).The structural basis for glycerol permeation by human AQP7.Science Bulletin,66(15).
MLA	Zhang L.,et al."The structural basis for glycerol permeation by human AQP7".Science Bulletin 66.15(2021).