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The 1 chain structure of human Aquaporin 1 1ih5



Aquaporin-1 (AQP1) was first discovered in human red blood cell membranes by Gheorghe Benga's research group in 1986.[1] However, it was only known to be a novel protein and its function was unknown. Initially AQP1 was coined CHIP28 for CHannel forming Integral membrane Protein of 28 kDa. It was'nt until 1991, Peter Agres research group discovered the functional characteristics of AQP1. In 1993, CHIP23 was renamed AQP1. Since then, 12 other isoforms of aquaporin-1 have been discovered and each have been classified under the family known as Aquaporins.[2]

Aquaporins are integral membrane proteins that specialize in the regulation of cellular water flow across the cell membrane.[3] This process is vital for any living organism to sustain proper physiological conditions and aquaporins are necessary to sustain this process (i.e. osmosis alone could not provide a sufficient flow of water). Extensive research on the function of aquaporins have been implemented into many separate types of cell membranes. Such membranes are from brain cells, kidney cells, muscle cells, red blood cells, and heart cells.

Water selective aquaporins are AQP1, -2, -4, -5, -6, -8, -12, and -0. A subgroup of aquaporins called aquaglycerporins allow the passage of small solutes such as glycerol, urea, and ammonia. Aquaglyceroporins are AQP3, -7, -9, and -10.[2]

Aquaporin-1 Structure

Aquaporin-1 is an integral membrane protein that is considered to have an "open" structure. Despite being "open", AQP1 has a high selectivity for the bidirectional transport of water, that even excludes small molecules such as hydrogen ions. AQP1 is formed as a tetramer in vivo, with each AQP1 monomer unit capable of transportation at a rate of ~2 trillion water molecules per second.[4]

Side view of AQP1 tetramer.  Available from:
Side view of AQP1 tetramer. Available from: Aquaporin-Sideview.png

An AQP1 monomer unit contains six highly tilted transmembrane α-helices and two internal α-helices, oriented in the form of a barrel. The transmembrane α-helices thread through the membrane so as to expose both the N- and the C-terminus to the inner cytoplasm. The aqueous pathway within the monomer unit is characterized by a narrow curvilinear pore that is ~4.0Å in diameter, ~18Å in length, and bends ~25 degrees as it transverses the membrane.[4] The curvilinear pore is a size selective pathway for water that excludes other larger and smaller molecules. The entrances to the aqueous pathway are mostly lined with polar and charged residues. Conversely, the interior of the aqueous pathway is mostly constituted by nonpolar residues. This feature allows for a relatively noninteracting pathway for the diffusion of water.

The N- and C-terminal halves of AQP1 are tandem repeats that contain a conserved tripeptide sequence.[4] Each terminal half is composed of three tilted transmembrane α-helices and a short α-helix adjacent to the conserved NPA motif. The two halves are connected through transmembrane 3 (TM3) and TM4 by a . The location of the two NPA tripeptide sequences define the apex of the curvilinear pathway (N76 & N192), which is located about the center of the membrane. This orientation of helices allows for a sufficient amount of noncovalent interactions to induce stability. Interactions between helices are dominantly hydrophobic. However, hydrogen-bond interactions have also been suggested to increase stability.

AQP1 takes the form of a tetramer in vivo. The Quaternary interactions between monomeric units are both hydrophobic and polar. Within the membrane, monomer interactions are dominantly hydrophobic. Whereas hydrogen-bonding dominates nocovalent interactions outside the membrane. The transmembrane α-helices of each monomer are oriented so define the interior of the AQP1 monomer (i.e. these helices face the other monomer units). are defined as the membrane exposed exterior face.[4]

Aquaporin-1 Regulation

Aquaporin channels may be subject to intense short term regulation via signal transduction. Transducers act as extracellular signal molecules that induce a response from membrane proteins. Protein Kinase C (PKC) has been documented as a common signal transducer among the aquaporins. One study suggests the positive relationship between PKC and AQP1.[5] In the presence of PKC, AQP1 was reported to have increased aqueous permeability. Phosphorylation of the amino acid on the AQP1 protein by PKC is attributed to the increased permeability. The increased activity of AQP1 in the presence of PKC may contribute to the stimulation of physiological processes that are modulated by AQP1 such as endothelial permeability, angiogenesis, and urea concentration.


  1. Benga G. The first discovered water channel protein, later called aquaporin 1: molecular characteristics, functions and medical implications. Mol Aspects Med. 2012 Oct-Dec;33(5-6):518-34. doi: 10.1016/j.mam.2012.06.001., Epub 2012 Jun 15. PMID:22705445 doi:
  2. 2.0 2.1 Rutkovskiy A, Valen G, Vaage J. Cardiac aquaporins. Basic Res Cardiol. 2013 Nov;108(6):393. doi: 10.1007/s00395-013-0393-6. Epub 2013, Oct 25. PMID:24158693 doi:
  3. Conner MT, Conner AC, Bland CE, Taylor LH, Brown JE, Parri HR, Bill RM. Rapid aquaporin translocation regulates cellular water flow: mechanism of hypotonicity-induced subcellular localization of aquaporin 1 water channel. J Biol Chem. 2012 Mar 30;287(14):11516-25. doi: 10.1074/jbc.M111.329219. Epub, 2012 Feb 9. PMID:22334691 doi:
  4. 4.0 4.1 4.2 4.3 Ren G, Reddy VS, Cheng A, Melnyk P, Mitra AK. Visualization of a water-selective pore by electron crystallography in vitreous ice. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1398-403. Epub 2001 Jan 30. PMID:11171962 doi:10.1073/pnas.041489198
  5. Zhang W, Zitron E, Homme M, Kihm L, Morath C, Scherer D, Hegge S, Thomas D, Schmitt CP, Zeier M, Katus H, Karle C, Schwenger V. Aquaporin-1 channel function is positively regulated by protein kinase C. J Biol Chem. 2007 Jul 20;282(29):20933-40. Epub 2007 May 23. PMID:17522053 doi:

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