MCB Sept23 2019 Membrane Structuremcb5068.wustl.edu/MCB/Lecturers/Huettner/2019 Membrane... ·...
Transcript of MCB Sept23 2019 Membrane Structuremcb5068.wustl.edu/MCB/Lecturers/Huettner/2019 Membrane... ·...
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MembraneStructure
lipidandproteincomponentsofbiologicalmembranes
JimHuettner
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LectureOverview
• History• Lipidcomponentsandasymmetry• Bioactivelipidmetabolites• Membraneproteins• Aminoacidsinthemembrane• Lipidmodifications• Subdomains(lipidrafts)
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EarlyHistory• Theabilityofoiltocalmthesurfaceofbodiesofwaterwas
recognizedinancienttimeshttps://www.youtube.com/watch?v=f2H418M3V6M
• 1700’s-BenFranklinperformedearlyexperimentswitholiveoilspreadingtoformamonolayeronapondsurface
• 1800’s-AgnesPockelsandLordRayleighcalculatedthethicknessofanoilmonolayerat13-16Angstroms
• 1900’s–LangmuirusedatroughsimilartoPockels’home-madeapparatustoanalyzesurfacetensionandconfirmtheearliermeasurements
WangDN,StieglitzH,MardenJ,TammLK.(2013)BenjaminFranklin,Philadelphia'sfavoriteson,wasamembranebiophysicist.BiophysJ.104:287-91.
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BilayerHistory
• 1925-GorterandGrendelcalculatethatRBCmembraneshaveenoughlipidsfor2xthesurfacearea
• 1935-1960s–Davidson-Danielli-Robertsonmodelsenvisionedabilayerwithproteinscoatingtheinnerandoutersurface
• 1972–SingerandNicholson–FluidMosaicModel
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Summaryofmembranemodels
RobertsonJL.(2018)Thelipidbilayermembraneanditsproteinconstituents.JGenPhysiol.150:1472-1483.
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FluidMosaicModel
Lodishetal.,8thed.Fig.7.1
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LipidComponents
o Phosphoglycerides• PC–phosphatidylcholine• PE–phosphatidylethanolamine• PS–phosphatidylserine• PI-phosphatidylinositol
o Sphingolipids• sphingomyelin• galactocerebroside(glycolipids)
o Sterols• cholesterol
Amphipathicpolar,hydrophilicnon-polar,hydrophobic
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chemicalstructures
Lodishetal.,8thed.Fig.7.8
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phosphoglycerides
Albertsetal.,6thed.
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ω-6andω-3cis-unsaturatedFAs
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Sphingomyelin
Luckey,2nded.Figs.2.7&2.8
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Glycolipids
Albertsetal.,6thed.
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Cholesterol
Albertsetal.,6thed.
• Mostprevalentinsurfacemembrane(uptoabout25%)• Precursortobileacids,steroidhormonesandvitaminD• Interactswithandstabilizessaturatedacylchains(sphingolipids)• Broadenstemperaturerangeofphasetransitionfromgelstatetofluidstates
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LipidCompositionVaries
Albertsetal.,6thed.
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LipidMobility
Albertsetal.,6thed.
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DistributionfromMDsimulation
Luckey,2nded.Figs.8.7&8.8
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ThicknessandCurvature
Lodishetal.,8thed.Fig.7.11
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BilayerPolarity
Lodishetal.,8thed.Fig.7.5
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LeafletAsymmetry
Luckey,2nded.Fig.2.14
AnionicPSandPIaremoreprevalentinthecytoplasmicleaflet
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LeafletCompositionVariesSource/Location PC PE+PS SM cholesterol
Plasmamembrane(humanRBCs) 21 29 21 26
Myelin(humannerve) 16 37 13 34
Plasmamembrane(mungbean) 47 43 0 0
Innermitochondrialmembrane(plant) 42 38 0 0
Outermitochondrialmembrane(plant) 47 27 0 0
ERmembrane(rat) 60 25 3 7
Golgimembrane(rat) 51 26 8 13
Innermitochondrialmembrane(rat) 40 37 2 7
Outermitochondrialmembrane(rat) 54 31 2 11
Primaryleafletlocation Exo Cyto Exo Both
Lodishetal.,8thed.Table7.1Composition(mol%)
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EnzymaticModification
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Phospholipasesites
Lodishetal.,8thed.Fig.7.12
Enzymaticreleaseofbioactivemetabolites:• IP3anddiacylglycerolbyPLC• LysophospholipidsbyPLA1orPLA2• Arachidonicordocosahexaenoic
acidbyPLA2
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MembraneProteins
Albertsetal.,6thed.
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AcylModification
Albertsetal.,6thed.
C14 C16 C15farnesylorC20geranylgeranyl
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GPIanchor
Luckey,2nded.Fig.4.10
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AdditionalFeatures
Albertsetal.,6thed.
• Oxidizingextracellularenvironmentpromotesinter-andintra-chaindisulfidebonds
• Reducingintracellularenvironmentkeepscysteinesidechainsavailableforthioesterification
• Extracellularoligosaccharidemodification• Tendencyforanexcessofpositivelycharged
ArgandLyssidechainsinthecytoplasmicsegments
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TMHelixAminoAcidPrevalence
Luckey,2nded.Fig.6.25
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ΔGformembraneinsertion
Luckey,2nded.Fig.7.23
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InsertionSignalVariety
Luckey,2nded.Fig.7.25
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Lipidsubdomains(rafts)
Albertsetal.,6thed.
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LipidRaftsAlbertsetal.,6thed.
Luckey,2nded.Fig.1.9
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“Ballpark”Numbers• “Typical”membraneincludesmorethan100distinctlipids• Morethan500differentfattyacidshavebeenidentified• Lateralmobilityinliposomessimilartooliveoilandabout100
foldslowerthanformoleculesinwater• Inanimalcellsabout50-90%ofcholesterolisinthesurface
membrane• Lipid/Proteinratiovaries:80%L/20%Pinmyelin,
25%L/75%Pinmitochondrialinnermembrane
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AdditionalReading• vanMeerG,VoelkerDR,FeigensonGW.(2008)Membranelipids:wheretheyareandhowtheybehave.NatRevMolCellBiol.9:112-24.
• vanMeerG,deKroonAI.(2011)Lipidmapofthemammaliancell.JCellSci.124:5-8.
• SezginE,LeventalI,MayorS,EggelingC.(2017)Themysteryofmembraneorganization:composition,regulationandrolesoflipidrafts.NatRevMolCellBiol.18:361-374.
• JacobsonK,LiuP,LagerholmBC.(2019)TheLateralOrganizationandMobilityofPlasmaMembraneComponents.Cell.177:806-819.
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DiscussionPaperforWednesday
ShiZ,GraberZT,BaumgartT,StoneHA,CohenE.(2018)CellMembranesResistFlow.Cell.175:1769-1779.
GrovesJT.(2019)MembraneMechanicsinLivingCells.DevCell.48:15-16.(abriefintro/reviewoftheShietal.paper)