6n1g

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Crystal structure of Aquaglyceroporin AQP7

Structural highlights

6n1g is a 4 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 3.995Å
Ligands:GOL
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

Xenopus oocytes expressing human aquaporin-7 (AQP7) exhibit greater osmotic water permeability and (3)H-glycerol uptake vs. those expressing the bacterial glycerol facilitator GlpF. AQP7-expressing oocytes exposed to increasing extracellular [glycerol] under isosmolal conditions exhibit increasing swelling rates, whereas GlpF-expressing oocytes do not swell at all. To provide a structural basis for these observed physiological differences, we performed X-ray crystallographic structure determination of AQP7 and molecular-dynamics simulations on AQP7 and GlpF. The structure reveals AQP7 tetramers containing two monomers with 3 glycerols, and two monomers with 2 glycerols in the pore. In contrast to GlpF, no glycerol is bound at the AQP7 selectivity filter (SF), comprising residues F74, G222, Y223, and R229. The AQP7 SF is resolved in its closed state because F74 blocks the passage of small solutes. Molecular dynamics simulations demonstrate that F74 undergoes large and rapid conformational changes, allowing glycerol molecules to permeate without orientational restriction. The more rigid GlpF imposes orientational constraints on glycerol molecules passing through the SF. Moreover, GlpF-W48 (analogous to AQP7-F74) undergoes rare but long-lasting conformational changes that block the pore to H2O and glycerol.

Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF.,Moss FJ, Mahinthichaichan P, Lodowski DT, Kowatz T, Tajkhorshid E, Engel A, Boron WF, Vahedi-Faridi A Front Physiol. 2020 Jun 30;11:728. doi: 10.3389/fphys.2020.00728. eCollection, 2020. PMID:32695023[5]

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

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Citations
3 reviews cite this structure
Carbon dioxide transport across membranes.
Michenkova et al. (2021)
2 more
5 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. ↑ Moss FJ, Mahinthichaichan P, Lodowski DT, Kowatz T, Tajkhorshid E, Engel A, Boron WF, Vahedi-Faridi A. Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF. Front Physiol. 2020 Jun 30;11:728. doi: 10.3389/fphys.2020.00728. eCollection, 2020. PMID:32695023 doi:http://dx.doi.org/10.3389/fphys.2020.00728

Contents


PDB ID 6n1g

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