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Sideview of Aquaporin 1 (AQP1) Channel

Aquaporins are a class of integral membrane proteins or more commonly referred to as a class of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. Image File history File links Broom_icon. ... Image File history File links Download high resolution version (800x749, 364 KB) Summary Sideview of Aquaporin 1 Channel (PDB ID, [1J4N http://www. ... Image File history File links Download high resolution version (800x749, 364 KB) Summary Sideview of Aquaporin 1 Channel (PDB ID, [1J4N http://www. ... An Integral Membrane Protein (IMP) is a protein molecule (or assembly of proteins) that is permanently attached to the biological membrane. ... Look up cell membrane in Wiktionary, the free dictionary. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the...

Genetic defects involving aquaporin genes have been associated with several human diseases. The 2003 Nobel Prize in Chemistry was awarded to Peter Agre for the discovery of aquaporins and jointly to Roderick MacKinnon for his work on the structure and operation of ion channels. For a non-technical introduction to the topic, see Introduction to Genetics. ... This is a list of Nobel Prize laureates in Chemistry from 1901 to 2006. ... Peter Agre (born January 30, 1949) is an American biologist who was awarded the 2003 Nobel Prize in Chemistry (which he shared with Roderick MacKinnon) for his discovery of aquaporins. ... Roderick MacKinnon (born 19 February 1956 in Burlington, Massachusetts) is a professor of Molecular Neurobiology and Biophysics at Rockefeller University who in 2003 was awarded the Nobel Prize in Chemistry for his work on the structure and operation of ion channels. ...

Function

Aquaporins selectively conduct water molecules in and out, while preventing the passage of ions and other solutes. Also known as water channels, aquaporins are membrane pore proteins. Aquaporins are commonly composed of four (typically) identical subunit proteins in mammals, with each monomer acting as a water channel. Impact from a water drop causes an upward rebound jet surrounded by circular capillary waves. ... 3D (left and center) and 2D (right) representations of the terpenoid molecule atisane. ... This article is about the electrically charged particle. ...

Water molecules traverse through the pore of the channel in single file. The presence of water channels increases membrane permeability to water.

Many human cell types express them, as do certain bacteria and many other organisms, such as plants for which it is essential for the water transport system. Biological tissue is a collection of interconnected cells that perform a similar function within an organism. ... Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ... “Life on Earth” redirects here. ...

History

In most cells, water moves in and out by diffusion through the lipid component of cell membranes. Due to the relatively high water permeability of some epithelial cells it was long suspected that some additional mechanism for water transport across membranes must exist, but it was not until the discovery of the first aquaporin, ‘aquaporin-1’ (originally known as CHIP), was reported by Peter Agre, then of Johns Hopkins University and now a professor and administrator at Duke University. The discovery of this first aquaporin took place in 1992. In zootomy, epithelium is a tissue composed of a layer of cells. ... Peter Agre (born January 30, 1949) is an American biologist who was awarded the 2003 Nobel Prize in Chemistry (which he shared with Roderick MacKinnon) for his discovery of aquaporins. ... The Johns Hopkins University, founded in 1876, is a private institution of higher learning located in Baltimore, Maryland, United States. ... Duke University is a private coeducational research university located in Durham, North Carolina, USA. Founded by Methodists and Quakers in the present-day town of Trinity in 1838, the school moved to Durham in 1892. ... Year 1992 (MCMXCII) was a leap year starting on Wednesday (link will display full 1992 Gregorian calendar). ...

The pioneering discoveries and research on water channels by Agre and his colleagues resulted in the presentation of a Nobel Prize in Chemistry to Agre in 2003. In 2000, together with other research teams, Agre reported the first high-resolution images of the three-dimensional structure of an aquaporin, viz. aquaporin-1. Further studies using supercomputer simulations have identified the pathway of water as it moves through the channel and demonstrated how a pore can allow water to pass without the passage of small solutes. The Nobel Prizes (Swedish: ) are awarded for Physics, Chemistry, Literature, Peace, and Physiology or Medicine. ... A supercomputer is a computer that led the world (or was close to doing so) in terms of processing capacity, particularly speed of calculation, at the time of its introduction. ...

Structure

Aquaporins are made up of six transmembrane α-helices arranged in a right-handed bundle, with the amino and the carboxyl termini located on the cytoplasmic surface of the membrane. The amino and carboxyl halves of the sequence show similarity to each other, in what appears to be a tandem repeat. Some researches believe that this results from an early evolution event which saw the duplication of the half sized gene. There are also five interhelical loop regions (A – E) that form the extracellular and cytoplasmic vestibules. Loops B and E are hydrophobic loops which contain the highly, although not completely conserved Asn-Pro-Ala (NPA) motif, which overlap the middle of the lipid bilayer of the membrane forming a 3-D 'hourglass' structure where the water flows through. This overlap forms one of the two well-known channel constriction sites in the peptide, the NPA motif and a second and usually narrower constriction known as 'selectivity filter' or ar/R selectivity filter.

Aquaporins form tetramers in the cell membrane, and facilitate the transport of water and, in some cases, other small uncharged solutes, such as glycerol, CO₂, ammonia and urea across the membrane depending on the size of the pore. The different aquaporins contain differences in their peptide sequence which allows for the size of the pore in the protein to differ between aquaporins. The resultant size of the pore directly affects what molecules are able to pass through the pore, with small pore sizes only allowing small molecules like water to pass through the pore. However, the water pores are completely impermeable to charged species, such as protons, a property critical for the conservation of membrane's electrochemical potential. “Glycerine” redirects here. ... For alternative meanings see proton (disambiguation). ... Electrochemical potential is a thermodynamic measure that reflects energy from entropy and electrostatics and is typically invoked in molecular processes that involve diffusion. ...

NPA motif

Using computer simulations, it has been suggested that the orientation of the water molecules moving through the channel assures that only water passes between cells, due to the formation of a single line of water molecules. The water molecules move through the narrow channel by orienting themselves in the local electrical field formed by the atoms of the channel wall. Upon entering, the water molecules face with their oxygen atom down the channel. Midstream, they reverse orientation, facing with the oxygen atom up. This rotation of the water molecules in the pore is caused by the interaction of hydrogen bonds between the oxygen of the water molecule and the asparagines in the two NPA motifs. While passing through the channel, the single-file chain of water molecules streams through, always entering face down and leaving face up. The strictly opposite orientations of the water molecules keep them from conducting protons via the Grotthuss mechanism, while still permitting a fast flux of water molecules. ^[1] General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... For other articles using the abbreviation or acronym asn see ASN. Asparagine is one of the 20 most common natural amino acids on Earth. ... For alternative meanings see proton (disambiguation). ... The protonic defect migrates through the hydrogen bond network through a series of covalent bond cleavage/formation. ...

ar/R selectivity filter

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The ar/R (aromatic/arginine) selectivity filter is a tetrad that is formed by two amino acid residues from helices 2 (H2) and 5 (H5) and two residues from loop E (LE1 and LE2), found on either side of the NPA motif. The ar/R region is usually found towards the extracellular vestibule, approximately 8Å above the NPA motif and is often the narrowest part of the pore. The narrow pore acts to weaken the hydrogen bonds between the water molecules allowing the water to interact with the positively charged arginine, which also acts as a proton filter for the pore. Image File history File links Confused. ...

Aquaporins in mammals

There are thirteen known types of aquaporins in mammals, and six of these are located in the kidney, but the existence of many more is suspected. The most studied aquaporins are:

• Aquaporin 1
• Aquaporin 2
• Aquaporin 3
• Aquaporin 4

Water crosses the cell membrane by either diffusing through the phospholipid bilayer or by passing through special water channels. Most aquaporins appear to be exclusive water channels that will not allow permeation of ions or other small molecules. Some aquaporins - known as aquaglyceroporins - transport water plus glycerol and a few other small molecules. AQP1 is a widely expressed water channel, whose physiological function has been most thoroughly characterized in the kidney. ... AQP2 is found in the apical cell membranes of the kidneys collecting duct principal cells and in intracellular vesicles located throughout the cell. ... Aquaporin 3 is found in the basolateral cell membrane of principal collecting duct cells and provide a pathway for water to exit these cells. ... Sideview of Aquaporin 1 (AQP1) Channel Aquaporins are a class of integral membrane proteins or more commonly referred to as a class of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. ... A DPPC bilayer simulation Color scheme: PO4 = green, N(CH3)3 = violet, water = blue, terminal CH3 = yellow, O = red, glycol C = brown, chain C = grey In biology and chemistry, a lipid bilayer is a membrane or zone of membrane composed only of lipid. ...

Aquaporins 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 two routes for water to flow in these tissues, known as the; apoplastic and symplastic pathways. The presence of aquaporins in the cell membranes seems to serve to facilitate the transcellular symplastic pathway for water transport. When plant roots are exposed to mercuric chloride, which is known to inhibit aquaporins, the flow of water is greatly reduced while the flow of ions is not, supporting the view that there exists a mechanism for water transport independent of the transport of ions; aquaporins. Within a plant, the apoplast is the free diffusional space outside the plasma membrane. ... Apoplast and symplast are two related concept in plant biology. ...

Aquaporins in plants are separated into four main homologous subfamilies, or groups,

• Plasma membrane Intrinsic Protein (PIP)
• Tonoplast Intrinsic Protein (TIP)
• Nodulin-26 like Intrinsic Protein (NIP)
• Small basic Intrinsic Protein (SIP)

These four subfamilies have continued to be broken up into smaller evolutionary subgroups that are directly related to their DNA sequence specificity. 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.

The silencing of plant aquaporins has been linked to pore plant growth and even death of the plant.

Gating of Plant Aquaporins

The gating of aquaporins is carried out to stop the flow of water through the pore of the protein. This may be carried out for a number of reasons, i.e. plant contains low amounts of cellular water due to drought. 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 it has been seen that there are at least two forms of aquaporin gating. These are gating by the dephosphorylation of certain serine residues, which has been linked as a response to drought, and the protonation of specific histidine residues in response to flooding. The phosphorylation of an aquaporin has also been linked to the opening and closing of a plant in response to temperature.

PIPs

Plasma membrane intrinsic proteins are found, as their name suggests in the plasma membrane of plant cells. There are two PIP subgroups, PIP1 and PIP2, due to the distinct differences in their peptide sequence. PIP1s commonly have lower water channel activity than PIP2s although it is not understood why. Also not understood, but the water channel activity of PIP1s has been seen to increase when in the tetramer form with PIP2s.

Aquaporins and disease

There have been two clear examples of diseases identified as resulting from mutations in aquaporins:

• Mutations in the aquaporin-2 gene cause hereditary nephrogenic diabetes insipidus in humans.
• Mice homozygous for inactivating mutations in the aquaporin-0 gene develop congenital cataracts.

A small number of people have been identified with severe or total deficiency in aquaporin-1. Interestingly, they are generally healthy, but exhibit a defect in the ability to concentrate solutes in the urine and to conserve water when deprived of drinking water. Mice with targeted deletions in aquaporin-1 also exhibit a deficiency in water conservation due to an inability to concentrate solutes in the kidney medulla by countercurrent multiplication. For a non-technical introduction to the topic, see Introduction to Genetics. ... Diabetes insipidus (DI) is a disease characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. ... Homozygote cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ... To meet Wikipedias quality standards, this article or section may require cleanup. ...

In addition to its role in genetically determined nephrogenic diabetes insipidus, aquaporins also play a key role in acquired forms of nephrogenic diabetes insipidus (disorders that cause increased urine production). Acquired nephrogenic diabetes insipidus can result from impaired regulation of aquaporin-2 due to administration of lithium salts (as a treatment for bipolar disorder), low potassium concentrations in the blood (hypokalemia), high calcium concentrations in the blood (hypercalcemia), or a chronically high intake of water beyond the normal requirements (e.g. due to excessive habitual intake of bottled water or coffee). Diabetes insipidus (DI) is a disease characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. ... For other uses, see Bipolar. ...

Finally, it has been found that autoimmune reactions against aquaporin 4 produce Devic's disease^[2] Devics disease, also known as Devics syndrome, neuromyelitis optica (NMO), or optic-spinal MS, is an autoimmune, inflammatory disorder in which a persons own immune system attacks myelin of the neurons of the optic nerves and spinal cord. ...

References

1. ^ E Tajkhorshid et al. Control of the Selectivity of the Aquaporin Water Channel Family by Global Orientational Tuning. Science 296 525 (2002)
2. ^ NMO-IgG links to aquaporin 4 water channel[1]

• Peter Agre (2006). "The aquaporin water channels". Proceedings of the American Thoracic Society 3 (1): 5-13. PMID 16493146. 
• Overview at miami.edu
• Nobel Museum at nobel.se
• Overview at colostate.edu
• Niall Harrison at urchin.earth.li
• Function and presence of recently identified aquaporins at colostate.edu
• Knepper M, Nielsen S (2004). "Peter Agre, 2003 Nobel Prize winner in chemistry". J Am Soc Nephrol 15 (4): 1093-5. PMID 15034115. 
• Nielsen S, Frøkiaer J, Marples D, Kwon T, Agre P, Knepper M (2002). "Aquaporins in the kidney: from molecules to medicine". Physiol Rev 82 (1): 205-44. PMID 11773613. 

Additional images

Structure of Aquaporin Image File history File links Size of this preview: 743 × 600 pixel Image in higher resolution (1292 × 1043 pixel, file size: 1. ...

AQP1 Image File history File links No higher resolution available. ...

AQP channel Image File history File links Size of this preview: 800 × 481 pixel Image in higher resolution (921 × 554 pixel, file size: 85 KB, MIME type: image/png) (All user names refer to de. ...

External links

• Structure, Dynamics, and Function of Aquaporins at uiuc.edu
• Pictures and Movies of Aquaporins
• Calculated positions of aquaporins of known 3D structure in membrane
• Animation (MPEG file at nobel.se)
• AQUAporin at aquaporin.dk
• MeSH Aquaporins