targeting outside sp.pptx
TRANSCRIPT
IntracellularTarge>ngofNascentPolypep>des
Figure 14-10 Molecular Biology of the Cell (© Garland Science 2008)
MitochondriaaretheSitesofOxida>veATPProduc>on
Sugars Triglycerides
MitochondrialBiogenesis
• Mitochondriacontaintheirowngenomeandproteinsynthe3cmachinery(tRNAs,mRNAs,ribosomes,ini3a3onandelonga3onfactors,etc.)
• Mitochondriaarecomprisedofhundredsofdis3nctproteins,onlyahandfulofwhichareencodedinthemitochondrialgenome(variesbyspecies)
• MostmitochondrialproteinsareencodedinnuclearDNA,synthesizedinthecytosol,andimportedpost-transla3onallyintotheorganelle
MitochondriaPossess4Subcompartments
UseofinvitroSystemstoElucidateMitochondrialImportMechanisms
Figure 12-23 Molecular Biology of the Cell (© Garland Science 2008)
ProteinsareIncorporatedIntoMitochondriaViaSeveralDifferentRoutes
Targe>ngtotheMatrixRequiresanN-TerminalImportSequence
Figure 12-22 Molecular Biology of the Cell (© Garland Science 2008)
N-terminalImportSequencesFormAmphipathicαHelicesthatInteractwiththeTom20/22Receptor
HydrophobiccleW
ProteinImportintotheMatrixRequiresPassageThroughTwoSeparateMembraneTranslocons
ProteinsTraversetheTOMandTIMTransloconsinanUnfoldedState
Transloca>onintotheMatrixOccursatZonesofAdhesion
Figure 12-26 Molecular Biology of the Cell (© Garland Science 2008)
ProteinImportintotheMatrixRequiresATPHydrolysisandanIntactProtonGradient
AcrosstheInnerMembrane
Targe>ngtotheInnerMembraneOccursVia3Dis>nctRoutes
Oxa1-MediatedStop-Transfer-Mediated Tom70/Tim22/54-Mediated
Mul>-PassProteinsSingle-PassProteins
CytochromeoxidasesubunitCoxVa
ATPSynthaseSubunit9
ADP/ATPAn>porter
CytochromeB2 CytochromecHemeLyase
Targe>ngtotheIntermembranousSpaceOccursViaTwoDis>nctPathways
DirectDeliveryIMSpaceProtease
Figure 12-27 Molecular Biology of the Cell (© Garland Science 2008)
Targe>ngtotheOuterMembraneViatheSAMProteinComplex
(Sor3ngandAssemblyMachinery)
(β-Barrell)
Figure 12-8 Molecular Biology of the Cell (© Garland Science 2008)
NuclearTransport
• Bidirec>onal• SingleLargePoreComplexSpans2lipidbilayers• NuclearPoresmuchlargerthanothertranslocons
Figure 12-9c Molecular Biology of the Cell (© Garland Science 2008)
EMofTransverseSec>onShowingaSide-ViewthroughtwoNPCs
Figure 12-9b Molecular Biology of the Cell (© Garland Science 2008)
ScanningEMofNPCsasViewedfromtheNucleoplasm
Figure 12-9a Molecular Biology of the Cell (© Garland Science 2008)
StructureofaNuclearPoreComplex
Figure 12-10 Molecular Biology of the Cell (© Garland Science 2008)
GatedDiffusionBarrierModelofNuclearTransport
Meshworkofdisorderedproteindomains
containingFGrepeats
Figure 12-11 Molecular Biology of the Cell (© Garland Science 2008)
NuclearImportSignalsareHighlyDiverseinSequence
• Bindtodis>nctnuclearimportreceptors• Canbeanywhereintheproteinsequencebutprobablyresideonsurfacepatches• Somearenotyetiden>fied
Figure 12-12 Molecular Biology of the Cell (© Garland Science 2008)
GoldPar>clesCoatedwithPep>desContainingaNLSTraverseNPCs
Proteinsdonothavetobeunfoldedbeforetheytraversethenuclearpore
Figure 12-13 Molecular Biology of the Cell (© Garland Science 2008)
NuclearImportandExportSequencesareRecognizedbyDifferentMembersoftheSameReceptorFamily(Keryopherins)
Figure 12-14 Molecular Biology of the Cell (© Garland Science 2008)
Direc>onalityisConferredonNuclearTransportbyaGradientofRan-GDP/GTPAcrosstheNuclearEnvelope
Figure 12-15 Molecular Biology of the Cell (© Garland Science 2008)
NuclearImportandExportOperateViaReciprocalUseoftheRan-GDP/GTPConcentra>onGradient
