Membrane Structural Biology: With Biochemical and Biophysical Foundations

345 Pages·2008·38.611 MB·English

by  Luckey M.

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MEMBRANE STRUCTURAL BIOLOGY
MembraneStructuralBiologyprovidesasolidbackgroundinmembranebiochemistry
thatalsoincorporatestheapproachesofbiophysics,genetics,andcellbiologytoinves-
tigationsofmembranestructure,function,andgenesis.Itdescribesthemanytoolsof
currentmembraneresearch,includingdetergentsandmodelsystems,bioinformatics,
protein-foldingmethodology,crystallographyanddiffraction,andmolecularmodel-
ing. The beautifully detailed structures of membrane components are presented in
thecontextoftheclassesoffamiliesofmoleculestheyrepresent.Manycorrelations
between membrane research and human health are discussed, and key themes for
futureworkinmembranestructuralbiologyareidentified.
Written with remarkable clarity, this book appears at a time when membranes
have moved back into the scientific spotlight and provides a unique foundation for
advanced students and working scientists. The new high-resolution structures of
membrane proteins generate exciting insights into how they function. The predic-
tionthatuptoathirdoftheproteinsencodedinthegenomearemembraneproteins
hasspurredthedevelopmentofhigh-throughputtoolsfortheirstructuralanalysis,as
wellaspowerfulcomputationalapproachesforproteomicsandmodeling.Research
in membrane structural biology is poised to answer many basic and applied ques-
tions,andthiscutting-edgetextwillprovideasolidfoundationforallthoseworking
inthisfield.
MaryLuckeyisaprofessorintheDepartmentofChemistryandBiochemistryatSan
FranciscoStateUniversity.SheearnedherPh.D.inBiochemistryatUniversityofCali-
forniaBerkeleywiththefirstidentificationofanirontransportproteininthebacterial
outer membrane. Her postdoctoral work demonstrated the specificity of the E. coli
maltoporininproteoliposomes.Whilecontinuingresearchonmaltoporinstructure
andfunction,shehastaughtbiochemistryfor25years,includingthegraduate-level
membranebiochemistrycoursethatprovidedtheimpetusforthisbook.
i
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MEMBRANE
ii
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STRUCTURAL BIOLOGY
WITH BIOCHEMICAL
AND BIOPHYSICAL
FOUNDATIONS
MARY LUCKEY
San Francisco State University
iii
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CAMBRIDGEUNIVERSITYPRESS
Cambridge,NewYork,Melbourne,Madrid,CapeTown,
Singapore,Sa˜oPaulo,Delhi,Tokyo,MexicoCity
CambridgeUniversityPress
32AvenueoftheAmericas,NewYork,NY10013-2473,USA
www.cambridge.org
Informationonthistitle:www.cambridge.org/9780521856553
©MaryLuckey2008
Thispublicationisincopyright.Subjecttostatutoryexception
andtotheprovisionsofrelevantcollectivelicensingagreements,
noreproductionofanypartmaytakeplacewithoutthewritten
permissionofCambridgeUniversityPress.
Firstpublished2008
Reprinted2011(twice)
PrintedinCanadabyFriesens
AcatalogrecordforthispublicationisavailablefromtheBritishLibrary.
LibraryofCongressCataloginginPublicationData
Luckey,Mary
Membranestructuralbiology:withbiochemicalandbiophysicalfoundations/
MaryLuckey.
p.; cm.
Includesbibliographicalreferencesandindex.
ISBN978-0-521-85655-3(hardback)
1.Membranes(Biology) 2.Membranelipids. 3.Membraneproteins. I.Title.
[DNLM: 1.CellMembrane–physiology. 2.MembraneLipids–physiology.
3.MembraneProteins–physiology.QU350L941m2008]
QH601.L75 2008
571.6(cid:2)4–dc22 2007031145
ISBN 978-0-521-85655-3Hardback
CambridgeUniversityPresshasnoresponsibilityforthepersistenceoraccuracyof
URLsforexternalorthird-partyInternetWebsitesreferredtointhispublicationand
doesnotguaranteethatanycontentonsuchWebsitesis,orwillremain,accurateor
appropriate.
Thetitlepageshowshigh-resolutionstructuresofmembraneproteinsincorporated
intoasimulatedlipidbilayer.Theproteinsare,fromlefttoright:vitaminB12
transportersBtuCDwithBtuF,thelightharvesterLH2withsomechlorophylls,the
mechanosensitivechannelMscS,lactosepermease,BtuBfromtheoutermembrane,
theporedomainofKv1.2,aquaporin,andCa2+-ATPase.Substrates,includingions
andwatermolecules,areindicated.
KindlyprovidedbyJ.Gumbart,Y.Wang,A.Aksimentiev,E.Tajkhorshid,
andK.Schulten,TheoreticalandComputationalBiophysicsGroup
attheUniversityofIllinois,Urbana-Champaign.
iv
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Contents in Brief
Preface xi
1 Introduction 1
2 TheDiversityofMembraneLipids 13
3 ToolsforStudyingMembraneComponents:
DetergentsandModelSystems 42
4 ProteinsinorattheBilayer 68
5 BundlesandBarrels 102
6 FunctionsandFamilies 127
7 ProteinFoldingandBiogenesis 160
8 DiffractionandSimulation 191
9 MembraneEnzymesandTransducers 213
10 TransportersandChannels 241
11 MembraneProteinAssemblies 271
12 ThemesandFutureDirections 309
AppendixI:Abbreviations 315
AppendixII:Single-LetterCodesforAminoAcids 318
Index 319
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vi
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Contents
Preface pagexi 3 ToolsforStudyingMembraneComponents:
DetergentsandModelSystems 42
1 Introduction 1 Detergents 43
TypesofDetergents 43
GeneralFeaturesofMembranes 1
BOX3.1Surfactantsandsurface
Paradigm1:TheAmphiphilicMoleculesin
tension 43
MembranesAssembleSpontaneously
MechanismofDetergentAction 45
duetotheHydrophobicEffect 4
MembraneSolubilization 48
Paradigm2:TheFluidMosaicModel
LipidRemoval 50
DescribestheMembraneStructure 5
ModelMembranes 50
AShiftintheParadigm:Biomembranes
Monolayers 50
HaveLateralDomainsthatForm
PlanarBilayers 53
“Rafts” 8
BOX3.2Electrophysiology 53
AViewfortheFuture:DynamicProtein
PatchClamps 55
ComplexesCrowdtheMembrane
SupportedBilayers 57
InteriorandExtendItsBorders 9
LiposomesfromSUVstoGUVs 60
MixedMicellesandBicelles 63
2 TheDiversityofMembraneLipids 13 BlebsandBlisters 63
Nanodiscs 66
TheAcylChains 13
ComplexLipids 17
4 ProteinsinorattheBilayer 68
Phospholipids 17
Sphingolipids 20 ClassesofProteinsthatInteract
SterolsandLinearIsoprenoids 20 withtheMembrane 68
TheLipidBilayerMatrix 23 ProteinsattheBilayerSurface 69
StructureofBilayerLipids 24 Extrinsic/PeripheralMembrane
DiffusionofBilayerLipids 24 Proteins 69
BOX2.1Fluorescencetechniques 26 ReversibleInteractionsofPeripheral
LipidAsymmetryandMembrane ProteinswiththeLipidBilayer 76
Thickness 26 BOX4.1Bindingofligandstosurfaces 79
LipidPolymorphism 28 ProteinsandPeptidesthatInsert
LamellarPhase 28 intotheMembrane 84
HexagonalPhaseandtheAmphiphile Toxins 84
ShapeHypothesis 29 Colicins 85
CubicPhase 31 Peptides 87
MiscibilityofBilayerLipids 31 SecA:ProteinAcrobatics 88
BOX2.2Phasediagrams 31 ProteinsEmbeddedintheMembrane 90
LateralDomainsandLipidRafts 33 MonotopicProteins 90
Detergent-ResistantMembranes 36 IntegralMembraneProteins 90
DiversityofLipids 37 Protein–LipidInteractions 94
BOX2.3Nonlamellarphaselipidsand BOX4.2Electronparamagneticresonance 97
growthofE.coli 40 HydrophobicMismatch 98
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viii Contents
BiogenesisofMembraneProteins 170
5 BundlesandBarrels 102
ExportfromtheCytoplasm 170
HelicalBundles 102 BOX7.2Evidenceforcleavablesignal
Bacteriorhodopsin 102 sequencesinvolvedinprotein
PhotosyntheticReactionCenter 107 translocation 171
β-Barrels 113 BOX7.3Importofmitochondrialproteins 177
BOX5.1NMRdeterminationofmembrane IntegrationofNascentProteinsinto
proteinstructure 116 theMembrane 178
Porins 118 BOX7.4Cross-linkingtracesnascent
SpecificPorins 120 peptidesthroughthetransloconinto
IronReceptors 123 thebilayer 179
TopogenesisinMembraneProteins 184
6 FunctionsandFamilies 127 MisfoldingDiseases 187
MembraneEnzymes 127
8 DiffractionandSimulation 191
BOX6.1Surfacedilutioneffects 128
DiacylglycerolKinase 129 BacktotheBilayer 191
P450Cytochromes 130 LiquidCrystallography 192
TransportProteins 131 BOX8.1X-rayandneutronscattering 193
TransportClassificationSystem 132 LiquidCrystalTheory 193
SuperfamiliesofATPases 134 JointRefinementofX-RayandNeutron
ABCTransporterSuperfamily 134 DiffractionData 194
GroupTranslocation 135 ModelingtheBilayer 196
Symporters 137 SimulationsofLipidBilayers 196
Antiporters 138 MolecularDynamics 197
IonChannels 138 BOX8.2Moleculardynamicscalculations 198
MembraneReceptors 139 MonteCarlo 202
NicotinicAcetylcholineReceptor 139 LipidsObservedinX-RayStructures
G-ProteinCoupledReceptors 140 ofMembraneProteins 203
BioinformaticsToolsforMembrane TheCrystallographer’sArt 207
ProteinFamilies 141 MembraneSimulations 210
PredictingTMSegments 141
BOX6.2Bioinformaticsbasics 142 9 MembraneEnzymesandTransducers 213
HydrophobicityPlots 143
OrientationofMembraneProteins 143 Enzymes 214
ThePositive-InsideRule 144 OMPLA 214
BOX6.3Makingandtestinghydrophobicity ProstaglandinH2Synthase 216
plots 144 BOX9.1Mechanismofactionof
GenomicAnalysisofMembrane prostaglandinH2synthase 218
Proteins 145 FormateDehydrogenase 222
BOX6.4StatisticalmethodsforTM Transducers 226
prediction 148 Rhodopsin,aGPCR 227
Helix–HelixInteractions 154 BOX9.2Efficiencyoflight-inducedsignal
ProteomicsofMembraneProteins 156 transduction 229
β-Barrels 157 BOX9.3NumberingTMhelices 231
MechanosensitiveIonChannels 235
7 ProteinFoldingandBiogenesis 160
10 TransportersandChannels 241
ProteinFolding 161
Foldingα-HelicalMembraneProteins 162 Transporters 241
BOX7.1Energeticsoffoldingandinsertion LacYandGlpT 242
ahydrophobicα-helixintothe MitochondrialADP/ATPCarrier 249
bilayer 164 Channels 253
FoldingStudiesofβ-BarrelMembrane AquaporinsandGlyceroaquaporins 253
Proteins 167 PotassiumChannels 258
OtherFoldingStudies 169 CalciumATPase 264
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Contents ix
TripartiteDrugEffluxviaaMembrane
11 MembraneProteinAssemblies 271
VacuumCleaner 300
F1F0-ATPase/ATPSynthase 272 AcrB,aPeristalticPump 300
SubunitStructureandFunction 273 AcrA,aMembraneFusionProtein 302
RegulationoftheF1F0-ATPase 276 TolC,theChannel-Tunnel 304
CatalyticMechanismofaRotaryMotor 277
ComplexesoftheRespiratoryChain 279 12 ThemesandFutureDirections 309
Cytochromebc 279
1
Oligomerization 309
Cytochrome-cOxidase 284
ConformationalChanges 310
TheTranslocon 286
MotifsandPatterns 311
TheM.jannaschiiTranslocon
Conclusions 312
Structure 286
TheTranslocon–RibosomeComplex 288
AppendixI:Abbreviations 315
ABCTransportersandBeyond 290
TheVitaminB UptakeSystem 291
12
TransportacrosstheInnerMembrane 291 AppendixII:SingleLetterCodesforAmino
TransportacrosstheOuterMembrane 294 Acids 318
DrugEffluxSystems 296
Sav1866,anABCMultidrugTransporter 297
Index 319
EmrE,SmallbutPowerful 299