Aquaporin

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[[Image:3gd8.png|left|200px|thumb|Crystal Structure of Human Aquaporin 4, [[3gd8]]]]
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<StructureSection load='1h6i' size='350' side='right' scene='41/411407/Cv/3' caption='Human aquaporin 1, [[1h6i]]'>
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{{STRUCTURE_3gd8| PDB=3gd8 | SIZE=300| SCENE=Aquaporin/Cv/1 |right|CAPTION=Human Aquaporin 4, [[3gd8]] }}
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[[Aquaporins]] are channel producing proteins which regulate the flow of water across the cell membrane. They are made of α-helix bundles. Aquaglyceroporin (GLpf) conducts water and polyalcohols. The images at the left and at the right correspond to one representative aquaporin structure, ''i.e.'' the crystal structure of human aquaporin 4 ([[3gd8]]). The image shows the protein, 6 molecules of glycerol and one of beta-octylglucoside.
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== Function ==
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{{TOC limit|limit=2}}
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'''Aquaporins''' are channel producing proteins which regulate the flow of water across the cell membrane.<ref>PMID:14630322</ref><br />
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*'''Aquaporin-0''' functions as water channel in lens fibers.<br />
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*'''Aquaporin-1''' see details in [[Aquaporin-1]].<br />
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*'''Aquaporin-2''' function is to reabsorb water from urine in the kidney.<br />
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*'''Aquaporin-3''' function is to promote glycerol permeability across cell membrane.<br />
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*'''Aquaporin-4''' regulates water balance in the central nervous system.<br />
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*'''Aquaporin-5''' is implicated in the forming of saliva, tears and pulmonary secretions.<br />
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*'''Aquaporin-7''' regulates nutrient availability and signaling responding to cellular stress<ref>PMID:32631905</ref>
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*'''Aquaporin-10''' is expressed exclusively in adipocytes and participates in maintaining low glycerol content in them<ref>PMID:23382902</ref>
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*'''NIP-2 aquaporin''' Nodulin 26-like intrinsic protein is a plant Aquaporin<ref>PMID:34890456</ref>
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*'''TIP-2 aquaporin''' is permeable to water and ammonia<ref>PMID:29445244</ref>
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*'''Aquaporin-Z''' is a major water channel in bacteria.<br />
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*'''Aquaglycerolporin''' (GLpf) is a water channel which can transport glycerol, polyalcohols, urea and other small solutes.<br />
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== 3D Structures of Aquaporin ==
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== Disease ==
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[[3llq]] – Aqp – ''Agrobacterium tumefaciens''<br />
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Mutations in aquaporin-2 cause diabitis insipidus. Mutations in aquaporin-0 in mice cause congenital cataracts. Aquaporin-4 is the primary autoimmune target of neuromyelitis optica.
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[[2w1p]], [[2w2e]] – Aqp1 – ''Pischia pastoris''<br />
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[[2zz9]] – rAqp4 (mutant) – rat<br />
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[[2d57]] – rAqp4 – electron crystallography<br />
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[[3gd8]] – hAqp4 – human<br />
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[[3d9s]] – hAqp5<br />
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[[1h6i]], [[1ih5]] – hAqp1<br />
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[[3cll]], [[3cn5]], [[3cn6]] – sAqp SoPIP2 (mutant) – spinach<br />
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[[1z98]], [[2b5f]] - sAqp SoPIP2<br />
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[[2o9d]], [[2o9f]] – EcAqpZ (mutant) – ''Escherichia coli''<br />
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[[2o9e]], [[2o9g]] - EcAqpZ (mutant)+Hg<br />
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[[2abm]], [[1rc2]] - EcAqpZ<br />
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[[2c32]], [[1ymg]] – cAqp0 – cow<br />
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[[1j4n]] – cAqp1<br />
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[[2b6o]] – Aqp0 - electron crystallography – sheep<br />
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[[2evu]], [[2f2b]] – AqpM – ''Methanothermobacter marburgensis''<br />
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== Structural highlights ==
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== 3D Structures of Aquaglyceroporin ==
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<scene name='41/411407/Cv/4'>Aquaporins are made of α-helix bundles</scene>. The water transporting channel contains 2 restriction sites conferring an hourglass model to the channel. Two NPA motifs from opposite surfaces form one restriction. Another restriction is formed by a cluster of aromatic/arginine side chains which serves to weaken the hydrogen bonding between water molecules.
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== 3D Structures of Aquaporin ==
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[[Aquaporin 3D structures]]
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[[1lda]], [[1ldi]] – EcGLpf<br />
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</StructureSection>
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[[1ldf]] – EcGLpf (mutant)<br />
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[[3c02]] – GLpf – ''Plasmodium falciparum''<br />
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== Summary of AQP4 Function ==
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AQP4 is the most abundant of the of three water channels in the Central Nervous System (CNS), and its expression is upregulated in the astrocytes of the brain cortex and spinal cord [5]. AQP4 allows only water to pass through the channel, preventing the transport of any solute [4]. It also plays a role in the removal of “excess brain water in vasogenic brain edema and hydrocephalus” by an unknown mechanism of bulk excretion of water [2]. However, AQP4 “provides a major route for water entry into the brain through an intact blood–brain barrier” [2], which exacerbates cytotoxic brain edema [2]. In addition, due to AQP4’s short extracellular loop formed from a 310 helix, AQP4 is able to play a role in cell adhesion by interacting with other AQP4 molecules on adjacent cell membranes. Finally, AQP4 plays a role in cell migration. For example, glial-scarring was reduced in the brain following injury due to AQP4-facilitated migration [9], and a role in brain tumor metastases is hypothesized because of AQP4’s elevated expression in glioblastomas and the role of AQP proteins in tumor cell migration [10].
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== Higher Order Structure of AQP4 ==
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AQP4 is organized in the plasma membrane into structures called orthogonal arrays of particles (OAPs). These structures are comprised of both the M23 and M1 isoforms of AQP4, though M23 is specifically required for the formation of OAPs as the amino acid sequence of the N-terminus of the M1 isoform appears to prevent formation of OAPs [4]. The recognition of AQP4’s role in the formation and structure of OAPs has led to further understanding in several neuromuscular diseases, including Duchenne Muscular Dystrophy, and NMO (see “Role in Autoimmune Disorders” below). There is also evidence that the formation of OAPs is physiologically regulated [5].
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== Role in Autoimmune Disorder ==
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Clinical presentations of central nervous system (CNS) aquaporin-4 autoimmunity are consistent with neuromyelitis optica (NMO), and can include blindness and paraplegia. Previously, variants of the NMO phenotype were classified as differential presentations of Multiple Sclerosis (MS). The specific causes of CNS AQP4 autoimmunity are unknown. However, observations of two patients with brain metastases suggest that CNS AQP4 autoimmunity may develop as part of an immune response to cancer [7]. As is the case in many autoimmune disorders, treatment of CNS AQP4 autoimmunity with anti-inflammatories (such as corticosteroids) and antibody-depleting therapeutics (such as plasma exchange) have been effective at reducing symptoms. Therapies for NMO based on the role of CNS AQP4 autoimmunity await further experimentation of the disease model and cell culture systems. [8]
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==References==
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<references/>
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[[Category:Topic Page]]

Current revision

Human aquaporin 1, 1h6i

Drag the structure with the mouse to rotate

References

  1. ↑ Agre P, Kozono D. Aquaporin water channels: molecular mechanisms for human diseases. FEBS Lett. 2003 Nov 27;555(1):72-8. PMID:14630322
  2. ↑ Dai C, Charlestin V, Wang M, Walker ZT, Miranda-Vergara MC, Facchine BA, Wu J, Kaliney WJ, Dovichi NJ, Li J, Littlepage LE. Aquaporin-7 Regulates the Response to Cellular Stress in Breast Cancer. Cancer Res. 2020 Oct 1;80(19):4071-4086. PMID:32631905 doi:10.1158/0008-5472.CAN-19-2269
  3. ↑ Laforenza U, Scaffino MF, Gastaldi G. Aquaporin-10 represents an alternative pathway for glycerol efflux from human adipocytes. PLoS One. 2013;8(1):e54474. PMID:23382902 doi:10.1371/journal.pone.0054474
  4. ↑ Beamer ZG, Routray P, Choi WG, Spangler MK, Lokdarshi A, Roberts DM. Aquaporin family lactic acid channel NIP2;1 promotes plant survival under low oxygen stress in Arabidopsis. Plant Physiol. 2021 Dec 4;187(4):2262-2278. PMID:34890456 doi:10.1093/plphys/kiab196
  5. ↑ Lindahl V, Gourdon P, Andersson M, Hess B. Permeability and ammonia selectivity in aquaporin TIP2;1: linking structure to function. Sci Rep. 2018 Feb 14;8(1):2995. PMID:29445244 doi:10.1038/s41598-018-21357-2
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