6qzi

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Crystal structure of human Aquaporin 7 at 1.9 A resolution

Structural highlights

6qzi is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Ligands:GOL, PO4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AQP7_HUMAN Forms a channel that mediates water and glycerol transport across cell membranes at neutral pH (PubMed:9405233, PubMed:11952783, PubMed:30423801, PubMed:30420639). The channel is also permeable to urea (PubMed:9405233). Plays an important role in body energy homeostasis under conditions that promote lipid catabolism, giving rise to glycerol and free fatty acids. Mediates glycerol export from adipocytes. After release into the blood stream, glycerol is used for gluconeogenesis in the liver to maintain normal blood glucose levels and prevent fasting hypoglycemia. Required for normal glycerol reabsorption in the kidney (By similarity).[UniProtKB:O54794][1] [2] [3] [4]

Publication Abstract from PubMed

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 A 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.

Structural Basis for Glycerol Efflux and Selectivity of Human Aquaporin 7.,de Mare SW, Venskutonyte R, Eltschkner S, de Groot BL, Lindkvist-Petersson K Structure. 2019 Nov 29. pii: S0969-2126(19)30395-8. doi:, 10.1016/j.str.2019.11.011. PMID:31831212[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
3 reviews cite this structure
Aquaglyceroporin Modulators as Emergent Pharmacological Molecules for Human Diseases.
Pimpão et al. (2022)
2 more
6 other articles
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See Also

References

  1. ↑ Kondo H, Shimomura I, Kishida K, Kuriyama H, Makino Y, Nishizawa H, Matsuda M, Maeda N, Nagaretani H, Kihara S, Kurachi Y, Nakamura T, Funahashi T, Matsuzawa Y. Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation. Eur J Biochem. 2002 Apr;269(7):1814-26. doi: 10.1046/j.1432-1033.2002.02821.x. PMID:11952783 doi:http://dx.doi.org/10.1046/j.1432-1033.2002.02821.x
  2. ↑ Gotfryd K, Mosca AF, Missel JW, Truelsen SF, Wang K, Spulber M, Krabbe S, Helix-Nielsen C, Laforenza U, Soveral G, Pedersen PA, Gourdon P. Human adipose glycerol flux is regulated by a pH gate in AQP10. Nat Commun. 2018 Nov 12;9(1):4749. doi: 10.1038/s41467-018-07176-z. PMID:30420639 doi:http://dx.doi.org/10.1038/s41467-018-07176-z
  3. ↑ Mosca AF, de Almeida A, Wragg D, Martins AP, Sabir F, Leoni S, Moura TF, Prista C, Casini A, Soveral G. Molecular Basis of Aquaporin-7 Permeability Regulation by pH. Cells. 2018 Nov 10;7(11). pii: cells7110207. doi: 10.3390/cells7110207. PMID:30423801 doi:http://dx.doi.org/10.3390/cells7110207
  4. ↑ Kuriyama H, Kawamoto S, Ishida N, Ohno I, Mita S, Matsuzawa Y, Matsubara K, Okubo K. Molecular cloning and expression of a novel human aquaporin from adipose tissue with glycerol permeability. Biochem Biophys Res Commun. 1997 Dec 8;241(1):53-8. doi: 10.1006/bbrc.1997.7769. PMID:9405233 doi:http://dx.doi.org/10.1006/bbrc.1997.7769
  5. ↑ de Mare SW, Venskutonyte R, Eltschkner S, de Groot BL, Lindkvist-Petersson K. Structural Basis for Glycerol Efflux and Selectivity of Human Aquaporin 7. Structure. 2019 Nov 29. pii: S0969-2126(19)30395-8. doi:, 10.1016/j.str.2019.11.011. PMID:31831212 doi:http://dx.doi.org/10.1016/j.str.2019.11.011

Contents


PDB ID 6qzi

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