Membrane Structure lipid and protein components of biological membranes Jim Huettner
MembraneStructure
lipidandproteincomponentsofbiologicalmembranes
JimHuettner
LectureOverview
• History• Lipidcomponentsandasymmetry• Bioactivelipidmetabolites• Membraneproteins• Aminoacidsinthemembrane• Lipidmodifications• Subdomains(lipidrafts)
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.
BilayerHistory
• 1925-GorterandGrendelcalculatethatRBCmembraneshaveenoughlipidsfor2xthesurfacearea
• 1935-1960s–Davidson-Danielli-Robertsonmodelsenvisionedabilayerwithproteinscoatingtheinnerandoutersurface
• 1972–SingerandNicholson–FluidMosaicModel
Summaryofmembranemodels
RobertsonJL.(2018)Thelipidbilayermembraneanditsproteinconstituents.JGenPhysiol.150:1472-1483.
FluidMosaicModel
Lodishetal.,8thed.Fig.7.1
LipidComponents
o Phosphoglycerides• PC–phosphatidylcholine• PE–phosphatidylethanolamine• PS–phosphatidylserine• PI-phosphatidylinositol
o Sphingolipids• sphingomyelin• galactocerebroside(glycolipids)
o Sterols• cholesterol
Amphipathicpolar,hydrophilicnon-polar,hydrophobic
chemicalstructures
Lodishetal.,8thed.Fig.7.8
phosphoglycerides
Albertsetal.,6thed.
ω-6andω-3cis-unsaturatedFAs
Sphingomyelin
Luckey,2nded.Figs.2.7&2.8
Glycolipids
Albertsetal.,6thed.
Cholesterol
Albertsetal.,6thed.
• Mostprevalentinsurfacemembrane(uptoabout25%)• Precursortobileacids,steroidhormonesandvitaminD• Interactswithandstabilizessaturatedacylchains(sphingolipids)• Broadenstemperaturerangeofphasetransitionfromgelstatetofluidstates
LipidCompositionVaries
Albertsetal.,6thed.
LipidMobility
Albertsetal.,6thed.
DistributionfromMDsimulation
Luckey,2nded.Figs.8.7&8.8
ThicknessandCurvature
Lodishetal.,8thed.Fig.7.11
BilayerPolarity
Lodishetal.,8thed.Fig.7.5
LeafletAsymmetry
Luckey,2nded.Fig.2.14
AnionicPSandPIaremoreprevalentinthecytoplasmicleaflet
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%)
EnzymaticModification
Phospholipasesites
Lodishetal.,8thed.Fig.7.12
Enzymaticreleaseofbioactivemetabolites:• IP3anddiacylglycerolbyPLC• LysophospholipidsbyPLA1orPLA2• Arachidonicordocosahexaenoic
acidbyPLA2
MembraneProteins
Albertsetal.,6thed.
AcylModification
Albertsetal.,6thed.
C14 C16 C15farnesylorC20geranylgeranyl
GPIanchor
Luckey,2nded.Fig.4.10
AdditionalFeatures
Albertsetal.,6thed.
• Oxidizingextracellularenvironmentpromotesinter-andintra-chaindisulfidebonds
• Reducingintracellularenvironmentkeepscysteinesidechainsavailableforthioesterification
• Extracellularoligosaccharidemodification• Tendencyforanexcessofpositivelycharged
ArgandLyssidechainsinthecytoplasmicsegments
TMHelixAminoAcidPrevalence
Luckey,2nded.Fig.6.25
ΔGformembraneinsertion
Luckey,2nded.Fig.7.23
InsertionSignalVariety
Luckey,2nded.Fig.7.25
Lipidsubdomains(rafts)
Albertsetal.,6thed.
LipidRaftsAlbertsetal.,6thed.
Luckey,2nded.Fig.1.9
“Ballpark”Numbers• “Typical”membraneincludesmorethan100distinctlipids• Morethan500differentfattyacidshavebeenidentified• Lateralmobilityinliposomessimilartooliveoilandabout100
foldslowerthanformoleculesinwater• Inanimalcellsabout50-90%ofcholesterolisinthesurface
membrane• Lipid/Proteinratiovaries:80%L/20%Pinmyelin,
25%L/75%Pinmitochondrialinnermembrane
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.
DiscussionPaperforWednesday
ShiZ,GraberZT,BaumgartT,StoneHA,CohenE.(2018)CellMembranesResistFlow.Cell.175:1769-1779.
GrovesJT.(2019)MembraneMechanicsinLivingCells.DevCell.48:15-16.(abriefintro/reviewoftheShietal.paper)