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Aquaporins

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Aquaporin proteins

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Aquaporins

  1. 1. The Aquaporin WaterThe Aquaporin Water ChannelsChannels
  2. 2. OutlineOutline 2 What is an Aquaporin? Specie Distribution Structural Features Mechanism of Action Human Aquaporins Medical Aspects of AQPs Conclusion
  3. 3. Major Intrinsic Proteins (MIPs)Major Intrinsic Proteins (MIPs) Transmembrane protein family High sequence similarity Two types of channels: 1) Aquaporins 2) Glycerol Facilitators 3
  4. 4. What is an Aquaporin?What is an Aquaporin? Six transmembrane helices joined together Found in all life forms Allow efficient permeation of water High specificity for water Highly conserved 4
  5. 5. 5
  6. 6. DiscoveryDiscovery Isolated from RBCs by Peter Agre in1992 Termed as Aquaporins 6
  7. 7. Species DistributionSpecies Distribution 13 known types in Mammals GlpF and AQPZ in E.coli 5 subfamilies in Plants (PIP,TIP, NIP, XIP, SIP) Human AQPs – 10 different genes Aquaporin family: (AQPs) and (AQGPs) 7
  8. 8. Bacterial AquaporinsBacterial Aquaporins Trp,Arg,Phe form constriction Two classes of bacterial AQP ◦ AQPZ : An explicit water channel ◦ GlpF : Transport glycerol 8
  9. 9. Structural Features of AquaporinsStructural Features of Aquaporins 9 Six transmembrane helices C and N terminals Extracellular loop A, C and E Intracellular loop B and D Highly conserved NPA motif
  10. 10. The NPA MotifThe NPA Motif 10 Asp-Pro-Ala Highly conserved amino acid motif
  11. 11. Hourglass FoldHourglass Fold Loop B and E fold into membrane and form Hourglass Fold Wide external openings to the channel with a narrow central constriction form the functional water pore 11
  12. 12. 12
  13. 13. Ar/R Selectivity FilterAr/R Selectivity Filter Cluster of amino acids help bind to water Prevent other molecules to enter membrane Tetrad:Two residues from helices 2 (H2) and 5 (H5) and two residues from loop E (LE1) and (LE2) 13
  14. 14. Role of AquaporinsRole of Aquaporins Increase rate of water transport Prevent other molecules to enter in membrane Symplastic movement of water in plants Water transport in prokaryotes (AQPZ) 14
  15. 15. Mechanism of ActionMechanism of Action 15 Water molecules orient themselves as Single-File H bonded chain Water interacts with NPA and rotated at 180˚ Fast flux is maintained Low Activation energy needed
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  17. 17. Human AquaporinsHuman Aquaporins 17
  18. 18. Aquaporins and DiseaseAquaporins and Disease AQP-2 gene: Hereditary Nephrogenic Diabetes Insipidus AQP-4 gene: Devic's Disease AQP-0 gene: Congenital Cataracts in mice 18
  19. 19. ConclusionConclusion AQPs are: • Highly conserved • Of Supreme importance • Plumbing system of cell 19
  20. 20. Future InsightsFuture Insights Much to learn yet… Design therapeutic models More technology and research work needed 20
  21. 21. ReferencesReferences  http://www.aquaporins.org/  http://www.wikidoc.org/index.php/Aquaporin_1  http://en.allexperts.com/e/a/aq/aquaporin.htm  http://www.pharmainfo.net/reviews/aquaporins-secret-highways-water- transport  http://www.danfoss-aquaz.com/aquaporins.asp  http://www.bio.miami.edu/~cmallery/150/memb/water.channels.htm 21

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