The structural basis for glycerol permeation by human AQP7
2021-08-15
发表期刊SCIENCE BULLETIN (IF:18.8[JCR-2023],15.8[5-Year])
ISSN2095-9273
EISSN2095-9281
卷号66期号:15页码:1550-1558
DOI10.1016/j.scib.2020.12.006
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 angstrom. 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. (c) 2021 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.
关键词Glycerol transportation Aquaglyceroporins Glycerol metabolism Structural biology
收录类别SCIE ; EI
语种英语
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000684396500013
出版者ELSEVIER
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127988
专题iHuman研究所_科学装置(X)_膜蛋白同步辐射线站
通讯作者Li, Yan; Zhou, Lu; Cao, Yu
作者单位
1.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol, Shanghai 201210, Peoples R China;
2.Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Inst Precis Med, Shanghai 200125, Peoples R China;
3.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China;
4.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed, Shanghai Key Lab Orthopaed Implant,Sch Med, Shanghai 200011, Peoples R China;
5.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 200433, Peoples R China
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GB/T 7714
Zhang, Li,Yao, Deqiang,Xia, Ying,et al. The structural basis for glycerol permeation by human AQP7[J]. SCIENCE BULLETIN,2021,66(15):1550-1558.
APA Zhang, Li.,Yao, Deqiang.,Xia, Ying.,Zhou, Fu.,Zhang, Qing.,...&Cao, Yu.(2021).The structural basis for glycerol permeation by human AQP7.SCIENCE BULLETIN,66(15),1550-1558.
MLA Zhang, Li,et al."The structural basis for glycerol permeation by human AQP7".SCIENCE BULLETIN 66.15(2021):1550-1558.
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