Aquaporin
Aquaporin | |||||||||
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TCDB 1.A.8 | | ||||||||
OPM superfamily | 7 | ||||||||
OPM protein | 2zz9 | ||||||||
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Aquaporins, also called water channels, are
The 2003 Nobel Prize in Chemistry was awarded jointly to Peter Agre for the discovery of aquaporins[6] and Roderick MacKinnon for his work on the structure and mechanism of potassium channels.[7]
Genetic defects involving aquaporin
History
The mechanism of facilitated water transport and the probable existence of water pores has attracted researchers since 1957.
Discovery
It was not until 1992 that the first aquaporin, 'aquaporin-1' (originally known as CHIP 28), was reported by Peter Agre, of Johns Hopkins University.[22] In 1999, together with other research teams, Agre reported the first high-resolution images of the three-dimensional structure of an aquaporin, namely, aquaporin-1.[23] Further studies using supercomputer simulations identified the pathway of water as it moved through the channel and demonstrated how a pore can allow water to pass without the passage of small solutes.[24] The pioneering research and subsequent discovery of water channels by Agre and his colleagues won Agre the Nobel Prize in Chemistry in 2003.[7] Agre said he discovered aquaporins "by serendipity." He had been studying the Rh blood group antigens and had isolated the Rh molecule, but a second molecule, 28 kilodaltons in size (and therefore called 28K) kept appearing. At first they thought it was a Rh molecule fragment, or a contaminant, but it turned out to be a new kind of molecule with unknown function. It was present in structures such as kidney tubules and red blood cells, and related to proteins of diverse origins, such as in fruit fly brain, bacteria, the lens of the eye, and plant tissue.[23]
However the first report of protein-mediated water transport through membranes was by Gheorghe Benga and others in 1986, prior to Agre's first publication on the topic.[25][26] This led to a controversy that Benga's work had not been adequately recognized either by Agre or by the Nobel Prize Committee.[27]
Function
Aquaporins are "the plumbing system for cells". Water moves through cells in an organized way, most rapidly in tissues that have aquaporin water channels.[28] For many years, scientists assumed that water leaked through the cell membrane, and some water does. However, this did not explain how water could move so quickly through some cells.[28]
Aquaporins selectively conduct
Water molecules traverse through the pore of the channel in single file. The presence of water channels increases membrane permeability to water. These are also essential for the water transport system in plants[30] and tolerance to drought and salt stresses.[31]
Structure
Aquaporin proteins are composed of a bundle of six transmembrane α-helices. They are embedded in the cell membrane. The amino and carboxyl ends face the inside of the cell. The amino and carboxyl halves resemble each other, apparently repeating a pattern of nucleotides. This may have been created by the doubling of a formerly half-sized gene. Between the helices are five regions (A – E) that loop into or out of the cell membrane, two of them hydrophobic (B, E), with an asparagine–proline–alanine ("NPA motif") pattern. They create a distinctive hourglass shape, making the water channel narrow in the middle and wider at each end.[29][32]
Another and even narrower place in the AQP1 channel is the "ar/R selectivity filter", a cluster of amino acids enabling the aquaporin to selectively let through or block the passage of different molecules.[33]
Aquaporins form
X-ray profiles show that aquaporins have two conical entrances. This hourglass shape could be the result of a natural selection process toward optimal permeability.[34] It has been shown that conical entrances with suitable opening angle can indeed provide a large increase of the hydrodynamic channel permeability.[34]
NPA motif
Aquaporin channels appear in simulations to allow only water to pass, as the molecules effectively queue up in single file. Guided by the aquaporin's local electric field, the oxygen in each water molecule faces forwards as it enters, turning around half way along and leaving with the oxygen facing backwards.[35] The arrangement of opposite-facing electrostatic potentials in the two halves of the channel prevents the flow of protons but permits water to pass freely.[36]
ar/R selectivity filter
The aromatic/arginine or "ar/R" selectivity filter is a cluster of amino acids that help bind to water molecules and exclude other molecules that may try to enter the pore. It is the mechanism by which the aquaporin is able to selectively bind water molecules and so to allow them through, and to prevent other molecules from entering. The ar/R filter is made of two amino acid groups from helices B (HB) and E (HE) and two groups from loop E (LE1, LE2), from the two sides of the NPA motif. Its usual position is 8 Å on the outer side of the NPA motif; it is typically the tightest part of the channel. Its narrowness weakens the hydrogen bonds between water molecules, enabling the arginines, which carry a positive charge, to interact with the water molecules and to filter out undesirable protons.[37]
Taxonomic distribution
In mammals
There are thirteen known types of aquaporins in mammals; six of these are located in the kidney,[38] but the existence of many more is suspected. The most studied aquaporins are compared in the following table:
Type | Location[39] | Function[39] |
---|---|---|
Aquaporin 1
|
|
Water reabsorption |
Aquaporin 2
|
|
Water reabsorption in response to ADH[40]
|
Aquaporin 3
|
|
Water reabsorption and glycerol permeability |
Aquaporin 4
|
|
Water reabsorption |
In plants
In plants, water is taken up from the soil through the roots, where it passes from the cortex into the vascular tissues. There are three routes for water to flow in these tissues, known as the apoplastic, symplastic and transcellular pathways. Specifically, aquaporins are found in the vacuolar membrane, in addition to the plasma membrane of plants; the transcellular pathway involves transport of water across the plasma and vacuolar membranes.
Aquaporins in plants are separated into four main homologous subfamilies, or groups:[44]
- Plasma membrane Intrinsic Protein (PIP)[45]
- Tonoplast Intrinsic Protein (TIP)[46]
- Nodulin-26 like Intrinsic Protein (NIP)[47]
- Small basic Intrinsic Protein (SIP)[48]
These five subfamilies have later been divided into smaller evolutionary subgroups based on their DNA sequence. PIPs cluster into two subgroups, PIP1 and PIP2, whilst TIPs cluster into 5 subgroups, TIP1, TIP2, TIP3, TIP4 and TIP5. Each subgroup is again split up into isoforms e.g. PIP1;1, PIP1;2. As isoforms nomenclature are historically based on functional parameters rather than evolutive ones, several novel propositions on plant aquaporines have been arisen with the study of the evolutionary relationships between the different aquaporins.[49] Within the various selection of aquaporin isoforms in plants, there are also unique patterns of cell- and tissue-specific expression.[41]
When plant aquaporins are silenced, the hydraulic conductance and photosynthesis of the leaf decrease.[50] When gating of plant aquaporins occurs, it stops the flow of water through the pore of the protein. This may happen for various reasons, for example when the plant contains low amounts of cellular water due to drought.[51] The gating of an aquaporin is carried out by an interaction between a gating mechanism and the aquaporin, which causes a 3D change in the protein so that it blocks the pore and, thus, disallows the flow of water through the pore. In plants, there are at least two forms of aquaporin gating: gating by the dephosphorylation of certain serine residues, in response to drought, and the protonation of specific histidine residues, in response to flooding. The phosphorylation of an aquaporin is involved in the opening and closing of petals in response to temperature.[52][53]
In Heteroconts
Specific aquaporins called Large Intrinsic Proteins (LIP)
In other organisms
Aquaporins have been discovered in the fungi Saccharomyces cerevisiae (yeast), Dictyostelium, Candida and Ustilago and the protozoans Trypanosoma and Plasmodium.[30]
Clinical significance
There have been two clear examples of diseases identified as resulting from mutations in aquaporins: mutations in the aquaporin-2
References
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External links
- Aquaporins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Animation (MPEGfile at nobel.se)
- Computational Biomolecular Dynamics Group. "Aquaporin movies and pictures". Max Planck Institute. Archived from the original on April 25, 2006. Retrieved 2008-01-23.
- Theoretical and Computational Biophysics Group. "Structure, Dynamics, and Function of Aquaporins". University of Illinois at Urbana-Champaign. Retrieved 2008-01-23.