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  Structural basis for glycerol efflux and selectivity of human Aquaporin 7.

de Maré, S. W., Venskutonytė, R., Eltschkner, S., de Groot, B. L., & Lindkvist-Petersson, K. (2020). Structural basis for glycerol efflux and selectivity of human Aquaporin 7. Structure, 28(2), 215-222. doi:10.1016/j.str.2019.11.011.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-7A1E-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-B7E2-D
Genre: Journal Article

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 Creators:
de Maré, S. W., Author
Venskutonytė, R., Author
Eltschkner, S., Author
de Groot, B. L.1, Author              
Lindkvist-Petersson, K., Author
Affiliations:
1Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society, ou_578573              

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Free keywords: AQP7; X-ray structure; adipocyte; aquaglyceroporin; aquaporin 7; atomistic MD simulations; glycerol channel; water
 Abstract: 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.

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Language(s): eng - English
 Dates: 2019-12-092020-02-04
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.str.2019.11.011
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Title: Structure
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 28 (2) Sequence Number: - Start / End Page: 215 - 222 Identifier: -