The Aquaporin Water The Aquaporin Water ChannelsChannels

OutlineOutline

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What is an Aquaporin?Specie DistributionStructural FeaturesMechanism of ActionHuman AquaporinsMedical Aspects of

AQPsConclusion

Major Intrinsic Proteins (MIPs)Major Intrinsic Proteins (MIPs)

Transmembrane protein family

High sequence similarity

Two types of channels:

1) Aquaporins2) Glycerol Facilitators

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What is an Aquaporin?What is an Aquaporin?

Six transmembrane helices joined together

Found in all life formsAllow efficient permeation of waterHigh specificity for waterHighly conserved

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DiscoveryDiscovery

Isolated from RBCs by Peter Agre in1992

Termed as Aquaporins

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Species DistributionSpecies Distribution

13 known types in MammalsGlpF and AQPZ in E.coli 5 subfamilies in Plants (PIP, TIP, NIP,

XIP, SIP)Human AQPs – 10 different genesAquaporin family: (AQPs) and

(AQGPs)

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Bacterial AquaporinsBacterial Aquaporins

Trp,Arg,Phe form constriction

Two classes of bacterial AQP◦ AQPZ : An

explicit water channel

◦ GlpF : Transport glycerol

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Structural Features of Structural Features of AquaporinsAquaporins

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Six transmembrane helices

C and N terminalsExtracellular loop A, C

and EIntracellular loop B and

DHighly conserved NPA

motif

The NPA MotifThe NPA Motif

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Asp-Pro-Ala Highly conserved

amino acid motif

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

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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)

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Role of AquaporinsRole of Aquaporins

Increase rate of water transportPrevent other molecules to enter

in membraneSymplastic movement of water

in plantsWater transport in prokaryotes

(AQPZ)

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Mechanism of ActionMechanism of Action

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Water molecules orient themselves as Single-File H bonded chain

Water interacts with NPA and rotated at 180˚

Fast flux is maintainedLow Activation energy needed

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Human AquaporinsHuman Aquaporins

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Aquaporins and DiseaseAquaporins and Disease

AQP-2 gene: Hereditary Nephrogenic Diabetes Insipidus

AQP-4 gene: Devic's DiseaseAQP-0 gene: Congenital Cataracts

in mice

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ConclusionConclusion

AQPs are:• Highly conserved• Of Supreme importance• Plumbing system of cell

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Future InsightsFuture Insights

Much to learn yet…Design therapeutic modelsMore technology and research

work needed

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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

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