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Protein degradation rate varies 100x

Protein degradation rate varies 100x Most have motifs marking them for polyubiquitination : taken to proteosome & destroyed Other signals for selective degradation include PEST & KFERQ PEST : found in many rapidly degraded proteins Deletion increases t 1/2 10x, adding PEST drops t 1/2 10x

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Protein degradation rate varies 100x

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  1. Protein degradationrate varies 100x • Most have motifs marking them for polyubiquitination: taken to proteosome & destroyed • Other signals for selective degradation include PEST & KFERQ • PEST : found in many rapidly degraded proteins • Deletion increases t1/2 10x, adding PEST drops t1/2 10x • Sometimes targets poly-Ub • Recent yeast study doesn’t support general role • KFERQ: cytosolic proteins with KFERQ are selectively taken up by lysosomes in chaperone-mediated autophagy under conditions of nutritional or oxidative stress.

  2. Protein degradationin bacteria Also highly regulated, involves chaperone-like proteins Lon (also in mito)

  3. Protein degradationin bacteria Also highly regulated, involves chaperone like proteins Lon Clp (also in chloroplasts)

  4. Protein degradationin bacteria Also highly regulated, involves chaperone like proteins Lon Clp FtsH in IM (also in cp and mito)

  5. PROTEIN TARGETING All proteins are made with an “address”which determines their final cellular location Addresses are motifs within proteins

  6. PROTEIN TARGETING All proteins are made with “addresses”which determine their location Addresses are motifs within proteins Remain in cytoplasm unless contain information sending it elsewhere

  7. PROTEIN TARGETING Targeting sequencesare both necessary& sufficient to send reporter proteins to new compartments.

  8. PROTEIN TARGETING 2 Pathways in E.coli http://www.membranetransport.org/ Tat: for periplasmic redox proteins & thylakoid lumen!

  9. 2 Pathways in E.coli • Tat: for periplasmic redox proteins & thylakoid lumen! • Preprotein has signal seqS/TRRXFLK

  10. 2 Pathways in E.coli • Tat: for periplasmic redox proteins & thylakoid lumen! • Preprotein has signal seqS/TRRXFLK • Make preprotein, folds • & binds cofactor in • cytosol

  11. 2 Pathways in E.coli • Tat: for periplasmic redox proteins & thylakoid lumen! • Preprotein has signal seqS/TRRXFLK • Make preprotein, folds • & binds cofactor in • cytosol • Binds Tat in • IM & is sent to • periplasm

  12. 2 Pathways in E.coli • Tat: for periplasmic redox proteins & thylakoid lumen! • Preprotein has signal seqS/TRRXFLK • Make preprotein, folds & binds cofactor in cytosol • Binds Tat in IM & is sent to periplasm • Signal seq is • removed in • periplasm

  13. 2 Pathways in E.coli http://www.membranetransport.org/ • Tat: for periplasmic redox proteins & thylakoid lumen! • Sec pathway • SecB binds preprotein • as it emerges from rib

  14. Sec pathway • SecB binds preprotein as it emerges from rib & prevents folding

  15. Sec pathway • SecB binds preprotein as it emerges from rib & prevents folding • Guides it to SecA, which drives it through SecYEG into periplasm using ATP

  16. Sec pathway • SecB binds preprotein as it emerges from rib & prevents folding • Guides it to SecA, which drives it through SecYEG into periplasm using ATP • In periplasm signal peptide is removed and protein folds

  17. Sec pathway part deux • SRP binds preprotein as it emerges from rib & stops translation • Guides rib to FtsY • FtsY & SecA guide it to SecYEG , where it resumes translation & inserts protein into membrane as it is made

  18. Periplasmic proteins with the correct signals (exposed after cleaving signal peptide) are exported by XcpQ system

  19. PROTEIN TARGETING Protein synthesis always begins on free ribosomes in cytoplasm

  20. 2 Protein Targeting pathways Protein synthesis always begins on free ribosomes in cytoplasm 1) proteins ofplastids, mitochondria, peroxisomes andnucleiare imported post-translationally

  21. 2 Protein Targeting pathways Protein synthesis always begins on free ribosomes In cytoplasm 1) proteins ofplastids, mitochondria, peroxisomes andnucleiare imported post-translationally made in cytoplasm, then imported when complete

  22. 2 Protein Targeting pathways Protein synthesis always begins on free ribosomes In cytoplasm 1) Post -translational: proteins ofplastids,mitochondria, peroxisomesandnuclei 2) Endomembrane system proteins are imported co-translationally

  23. 2 Protein Targeting pathways 1) Post -translational 2) Co-translational: Endomembrane system proteins are imported co-translationally inserted in RER as they are made

  24. 2 pathways for Protein Targeting 1) Post -translational 2) Co-translational: Endomembrane system proteins are imported co-translationally inserted in RER as they are made transported to final destination in vesicles

  25. SIGNAL HYPOTHESIS Protein synthesis always begins on free ribosomes in cytoplasm in vivo always see mix of free and attached ribosomes

  26. SIGNAL HYPOTHESIS Protein synthesis begins on free ribosomes in cytoplasm endomembrane proteins have "signal sequence"that directs them to RER Signal sequence

  27. SIGNAL HYPOTHESIS Protein synthesis begins on free ribosomes in cytoplasm endomembrane proteins have "signal sequence"that directs them to RER “attached” ribosomes are tethered to RER by the signal sequence

  28. SIGNAL HYPOTHESIS • Protein synthesis begins on free ribosomes in cytoplasm • Endomembrane proteins have"signal sequence"that directs them to RER • SRP (Signal Recognition Peptide) binds signal sequence when it pops out of ribosome & swaps GDP for GTP

  29. SIGNAL HYPOTHESIS • SRP (Signal Recognition Peptide) binds signal sequence when it pops out of ribosome & swaps GDP for GTP • 1 RNA & 7 proteins

  30. SIGNAL HYPOTHESIS • SRP binds signal sequence when it pops out of ribosome • SRP stops protein synthesis until it binds “docking protein”(SRP receptor) in RER

  31. SIGNAL HYPOTHESIS SRP stops protein synthesis until it binds “docking protein”(SRP receptor) in RER Ribosome binds Translocon & secretes protein through it as it is made

  32. SIGNAL HYPOTHESIS SRP stops protein synthesis until it binds “docking protein”(SRP receptor) in RER Ribosome binds Translocon & secretes protein through it as it is made BiP (a chaperone) helps the protein fold in the lumen

  33. SIGNAL HYPOTHESIS Ribosome binds Translocon & secretes protein through it as it is made secretion must be cotranslational

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