PT  - JOURNAL ARTICLE
AU  - Li Zhang
AU  - Deqiang Yao
AU  - Fu Zhou
AU  - Qing Zhang
AU  - Ying Xia
AU  - Qian Wang
AU  - An Qin
AU  - Jie Zhao
AU  - Dianfan Li
AU  - Lu Zhou
AU  - Yu Cao
TI  - The Structural Basis for Glycerol Permeation by human AQP7
AID  - 10.1101/858332
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 858332
4099  - http://biorxiv.org/content/early/2019/11/29/858332.short
4100  - http://biorxiv.org/content/early/2019/11/29/858332.full
AB  - Human glycerol channel AQP7 conducts glycerol release from adipocyte and entry into the cells in pancreatic islets, muscles and kidney tubule, and thus regulate 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 to the Ar/R filter and the bound glycerol molecule stabilized by R229. In vivo functional assay on human AQP7 as well as AQP3 and AQP10 demonstrated strong glycerol transportation activities at physiological condition. The human AQP7 structure reveals a fully closed conformation with its permeation pathway strictly confined by Ar/R filter at the exoplasmic side and the gate at the cytoplasmic side, and the dislocation of the residues at narrowest parts of glycerol pathway in AQP7 play a critical role in controlling the glycerol flux.