Structural Basis for Glycerol Efflux and Selectivity of Human Aquaporin 7.,Structure

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Structural Basis for Glycerol Efflux and Selectivity of Human Aquaporin 7.
Structure ( IF 4.4 ) Pub Date : 2019-12-09 , DOI: 10.1016/j.str.2019.11.011
Sofia W de Maré ₁ , Raminta Venskutonytė ₁ , Sandra Eltschkner ₁ , Bert L de Groot ₂ , Karin Lindkvist-Petersson ₁

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The aquaglyceroporin 7 (AQP7) facilitates permeation of glycerol through cell membranes and is crucial for lipid metabolism in humans. Glycerol efflux in human adipocytes is controlled by translocation of AQP7 to the plasma membrane upon hormone stimulation. Here we present two X-ray structures of human AQP7 at 1.9 and 2.2 Å resolution. The structures combined with molecular dynamics simulations suggest that AQP7 is a channel selective for glycerol and that glycerol may hamper water permeation through the channel. Moreover, the high resolution of the structures facilitated a detailed analysis of the orientation of glycerol in the pore, disclosing unusual positions of the hydroxyl groups. The data suggest that glycerol is conducted by a partly rotating movement through the channel. These observations provide a framework for understanding the basis of glycerol efflux and selectivity in aquaglyceroporins and pave the way for future design of AQP7 inhibitors.

中文翻译：

甘油流出的结构基础和人水通道蛋白的选择性7。

甘油水通道蛋白7（AQP7）促进甘油透过细胞膜的渗透，对于人类的脂质代谢至关重要。人脂肪细胞中的甘油外排受激素刺激后AQP7易位至质膜的控制。在这里，我们介绍了1.9和2.2Å分辨率的人类AQP7的两种X射线结构。结合分子动力学模拟的结构表明，AQP7是甘油的选择性通道，甘油可能会阻碍水通过通道的渗透。此外，结构的高分辨率有助于对甘油在孔中的取向进行详细分析，从而揭示了羟基的异常位置。数据表明甘油是通过通道中的部分旋转运动进行的。

更新日期：2019-12-11

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