Download - 第六章 细胞内膜系统 与蛋白质分选
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INTRACELLULAR COMPARTMENT AND PROTEINS SORTING
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RERER
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,:? ? ?
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signal sequencesorting receptor
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signal sequence15-60signal peptidasesignal patch
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signal sequence and signal patch
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-Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val-
-Leu-Ala-Leu-Lys-Leu-Ala-Gly-Leu-Asp-Ile-
+H3N-Met-Leu-Ser-Leu-Arg-Gln-Ser-Ile-Arg-Phe-Phe-Lys-Pro-Ala-Thr-Arg
-Thr-Leu-Cys-Ser-Ser-Arg-Tyr-Leu-Leu-
+H3N-Met-Val-Ala-Met-Ala-Met-Ala-Ser-Leu-Gln-Ser-Ser-Met-Ser-Ser-Leu-
Ser-Leu-Ser-Ser-Asn-Ser-Phe-Leu-Gly-Gln-Pro-Leu-Ser-Pro-Ile-Thr-Leu-
Ser-Pro-Phe-Leu-Gln-Gly-
-Ser-Lys-Leu-COO-
+H3N-Met-Met-Ser-Phe-Val-Ser-Leu-Leu-Leu-Val-Gly-Ile-Leu-Phe-Trp-Ala-
Thr-Glu-Ala-Glu-Gln-Leu-Thr-Lys-Cys-Glu-Val-Phe-Gln-
-Lys-Asp-Glu-Leu-COO-
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1gated transport2transmembrane transporttranslocator3vesicular transport
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coat
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3dyneinkinesinmyosin
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clathrinCOPICOPII
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KDEL, KDELCOP,
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(),(adapter),(dynamin)GTP
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50100nm180kDa3540kDa, --(triskelion), (three-legged protein),, (a) ;(b);(c) P401
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(adaptin):AP1AP2AP3AP1: AP1M6P,AP1AP2AP2: AP2()()AP3: , AP3AP3,
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Clathrin coated vesicles
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, (), , ,
, , , , , Hsp70, Ca2+ , Ca2+ , Ca2+ , , Ca2+ ,
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dynamin1.5nmpinch off,900, GTPGTP,GTP,
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COP I ( COP I ) COP,7:COP, COPCOPCOP escaped proteins
Cop I Vesicles
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Cop I and II VesiclesCOP I
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Lys-Asp-Glu-LeuKDELLys-Asp-Glu-LeuKDEL
SRPCLys-Lys-X-XCOP
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COP GTP,ARF,GDP,GTP,ARF-GTP,GDPGTP ARFGTPaseARFGDP,GTPGTPARFARFGTP COPARF CoA(fatty-acyl CoA)COP,CoACOPCOP, , ARFGTP
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COPSar1GTPSec23/Sec24Sec13/Sec31exit sitesCOP IICOP II[DE]X[DE] Asp-X-Glu COP
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GTPcoat-recruitment GTPaseGTPmonomeric GTPaseGguanine-nucleotide exchange factor, GEFGDPGTP GTPGTPase activating protein, GAPGTP GTPARFSAR 1ARFCOP ISAR 1COP II
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GTPGDPCOPIISAR1GDPGTPSAR 1SAR1Dphospholipase D
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Coat assemblyCOPSar1GSar1GDPGTP, Sec23Sec24,Sec13Sec31,ER,Sec16Sec23/Sec24Sec13/Sec31,COP
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, ???
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: SNARE soluble NSF attachment protein receptorJames Rothman,N-(N-ethylmaleimide-sensitive fusion protein,NSF)NSF(soluble NSF attachment protein,SNAPs)NSFSNAPs --- SNAPsSNARE NSF/ SNAPs,Rothman:SNAP(SNAP receptors)SNAREsSNAPs
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SNAREs20SNAREsv-SNAREst-SNAREs
v-t-SNAREsSNAREstrans-SNAREs complexes
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SNAREs in vesicle transportRothmanSNAREV-SNARET-SNARE V-SNARE, T-SNARE,
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NSF SNAREsATPadaptor proteinSNAREs
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SNAREsSNAREsSNAREs
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HIV fusion protein
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Rabs RabGTP Rabstargeting GTPaseGTP30RabsRabsRabsGTPGDPGTPSNAREsRabseffector Rab
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Rabs in docking
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Rab
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Bulk-phase endocytosis(Receptor mediated endocytosis, RME)caveolae
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coated pitsmolecular filter2%4Tyr-X-X-XPheLeuMetdynamin
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Clathrin coated piton the cytosolic face of a cell
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(pit); ; , , ; ,
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,(), : ,, , : ,(M6PLDL),, ,, :
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LDL ParticleLDL
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LDL22nm, 1500800500,LDL55 kDaB100(apolipoprotein B-100), (a)LDL, apo-B,LDL(b)
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LDL endocytosis(low-density lipoprotein, LDL) LDLLDLLDL
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Recycling of LDL receptors
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(1) LDL;(2); (3);(4)();(5)pH,LDL(); (6) ,; (7),;(8)LDL, (10),,LDL
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, , , ()(apotransferrin), Fe3+, (ferrotransferrin),pH, ,, , , , ,, , , ,
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LDL Endocytosis
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Transcytosis ,, , ,, , pH=6,()pH=7,FcpH=6IgGFc, pH=7Fc-IgG,IgG,
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SNARERabLDL
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constitutive exocytosis pathwayTGNdefault pathwayregulated exocytosis pathway
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K. R. Porter1945endoplasmic reticulumER,
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rough endoplasmic reticulumRERsmooth endoplasmic reticulumSERRER , SER,, RERSERER
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,
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ER
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RER
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SER
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ERERER60%40%ER3030-6-ribophorinRERP450SER
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(microsome) ,,
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ER-----
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, , ,
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----------- George Palade,(membrane-bounded ribosome), :,,, Colvin Redman David SabatiniRER(),
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RER,N-,;(b)RER,RER,
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G. Blobel1975(Signal hypothesis)N1999signal peptideN16~306-15start transfer sequence,
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AA Sequences of ER Signal Peptides : +H3N ; COO
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1975, G.Blobel B.Dobberstein ,(signal hypothesis),(1);(2)N-,,N-;(3),;(4),,,,
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signal recognition particleSRP67S RNARNP(ribonucleoprotein)[]SRPSPR receptorSRPSRP, stop transfer sequencePrtranslocatortranslocon3-4Sec61Sec613
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Translocation of soluble proteins across ER
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ERERmRNASRPSRP; ,SRPA,
SRP(), (protein-translocating channel) SRP SRP---mRNA,SRPGTPSRP,,,SRP,SRP,(),,,
,(signal peptidase),,
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SRPSRPSRP co-translation
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GTP SRPSRPG,, GTP-GDP, (translocon), GTP
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(internal signal peptides),N-,,SRP,,,,, SRP,,,,(a) ,,(b)(a),,,
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Insertion of a Multipass Transmembrane protein into the ER membrane
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42O-O-linked glycosylationSerThrHypOHN-N-N-linked glycosylationNH2N-
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N-CMP-GDP-UDP-N-dolichol phosphateAsn-X-SerAsn-X-Thr
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Protein glycosylation in RER
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ERER,ERERER,ER,
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COP IIexit siteshsp70ATP90%T
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BipBip (heavy-chain binding protein) ,IgGBip,Hsp70,BipBipDNA,BipBipERBipERER
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PTPP4506-
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, -6-,-1-,-6-,,-6--6-,
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,,,CDP-,
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(1)P-450;(2)P-450NADPH; (3)P-450;(4),
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18551889Golgi2050
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cis facetrans face1um4~8()(Golgi stack)
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The Golgi Apparatus
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60%40%ERER-
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cis Golgi networkCGNmedial Golgitrans Golgi networkTGN
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cis(TPP)trans12(NADP)(CMP)transCMP
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, , , 1RERERCOPIICGNmedial GdgiTGN
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ER
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:Lys-Asp-Glu-Leu-COO-KDELKDELERER, ER,, ER""ER
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ER,: , ER ; ,,, ;,(4a)(4b);,(6a)(6b)
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(constitutive secretory pathway), , (transport vesicles)(regulated secretory pathway), , ,, (secretory vesicles):;,200
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2O-
, , 3 RER , 5, 2N-22,
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34NCC56
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B, N- , (preproinsulin), 12,000, , (proinsulin),9,000, 84, , 51C
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KDEL,
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N-O-
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lysosomeC. de DuveB. Novikoff 1955
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H+PH
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0.2~0.5um60PH51primary lysosome
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2Secondary lysosomeautophagolysosome(phagolysosome)
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3residual body post-lysosome
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10
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, ,, ,
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6-(mannose 6-phosphate, M6P)transN-cis1~2N-M6Ptransclathrin
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(signal patch) , , , ,
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N- N-, N- N-,N-UDP-GlcNAc
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UDP N-(N-acetyglucosamineGlcNAc),
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Transport of newly synthesized hydrolases to lysosomes(early endosome)(late endosome), pH, ATPase-H+ H+ pH
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, ,M6P,, , pH, M6P, . , , , M6P, , ,
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, , , ,
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3-Tay-Sachs dieseaseAGM2 IIPompe-1,4-Gaucher- inclusion-cell diseaseN-M6P
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1998
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, 19143,.194319501980 19781980819922319801630 4CytomixisB 1998ProtoplasmaI19871985198621999
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Rhodin 19540.5umflavin40H2O2RH2+O2R+H2O2
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Peroxisome of hepatocyte
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- H2O21/4-A
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-Ser-Lys-Leu-COO-PTP
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1 2 3 4 forming facecis face trans face 1 AM6P B C D2 A B C D
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3Following organelles are all surrounded by double bio-membranes except AMitochondrion BChloroplast. CER. DNucleus. 4clathrin____ A. (endosome) B. C. D. E. 5. ____ A. B. C. D. E.
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6. v-SNAREs____ A. B. C. D. 7COP A. B. C. D.