lec7ER-ProteinTRans_Folding

Molecular Biology of the Cell

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Unformatted text preview: PROTEIN SORTING, DISTRIBUTION SECRETION & ENDOCYTOSIS SECRETION Chapter 15 Chapter Structural Components of Protein Structural Fig 3-2, MBOC4 Condensation Proteins Fig 2-65, MBOC4 Structural Components of Protein Structural Fig 3-2, MBOC4 Signal Hypothesis Signal 1. Signal sequence directs protein/ ribosomes to a translocator (with ribosomes the aide of an SRP) the 2. Peptide is translocated into the 2. ER lumen as it is being created ER -as RNA is being translated - co-translocation co-translocation 3. The signal sequence is cleaved 3. off leaving the complete protein in the lumen. in Note: where is the signal signal recognition sequence ? Fig 12-40, MBOC4 Protein Arrangements in Membranes Protein Protein Protein arrangement varies varies How do we How create these proteins? proteins? Fig 10-17, MBOC4 Synthesis of Multi-Pass Transmembrane Protein Synthesis Fig 12-50, MBOC4 Synthesis of Single-Pass Transmembrane Protein – N-terminal Start-transfer Sequence Protein Note the location of the ends of the peptide Requires a Stop and a Requires Start Transfer sequence sequence Stop-transfer sequence Stop-transfer anchors the protein to the transloctor. Translation continues in the cytosol in Fig 12-47, MBOC4 Synthesis of Single-Pass Transmembrane Protein – N-terminal Start-transfer Sequence Start-transfer Requires a Stop and a Requires Start Transfer sequence sequence Stop-transfer sequence Stop-transfer anchors the protein to the transloctor. Translation continues in the cytosol in Start transfer (SRS) is Start cleaved of and the result is single pass membrane membrane Note the location of the ends of the peptide Fig 12-47, MBOC4 Synthesis of Single-Pass Transmembrane Protein – Internal Start-transfer Sequence (A) Internal Note the location of the ends of the peptide Orientation of Start-Trasfer sequence Orientation determines on which sides of the membrane are the ends of the proteins proteins - still need a stop transfer sequence Negative charges first….then NH2 Negative end on the cytosol face of the ER membrane membrane Positive charges first…..COOH end is Positive in the cytosol Fig 12-48, MBOC4 Synthesis of Double-Pass Transmembrane Protein Synthesis Combination of Start and stop transfer sequences Fig 12-49, MBOC4 Synthesis of Multi-Pass Transmembrane Protein Synthesis Fig 12-50, MBOC4 N-linked Glycosylation of Proteins Proteins Always occurs on the Always Lumen side of the ER. Not on Cytosolic side Not because of its reducing nature nature N llinked because the inked glucose is attached to the NH2 group of an aspartic acid acid Fig 12-51, MBOC4 Glycosylation of Proteins Always occurs on the Always Lumen side of the ER. Not on Cytosolic side Not because of its reducing nature nature Fig 12-52, MBOC4 Creation of a Functional Protein Creation Protein folding and degradation are Protein important steps in regulation of production of active protein of Abnormally folded proteins can Abnormally accumulate and cause disease accumulate Alzheimer’s disease Bovine spongiform encephalopathy Bovine • (mad cow disease) Proteins Fold in ER Lumen Proteins Protein disulfide isomerase Breaks disulfide bonds; allows new ones to form Protein reaches lowest energy state Binding Protein (BiP) Binds to improperly folded proteins, retains in ER May help proteins refold to native conformation Protein glycosylation used to sort properly folded Protein proteins proteins Current View of Protein Folding (general) Protein folding is assisted by chaperones through a folding pathway pathway Molecular chaperones assist folding. Keeps protein on the “On Pathway” Keeps Heat shock proteins Heat Hsp 60 and Hsp 70 (BIP in ER) “ On Pathway”- correct folding On “Off Pathway”- incorrect folding Proteasome – final destination acts as a proteolytic trashcan proteolytic Fig 6-82, MBOC4 Proteasome 20s Proteasome 20s Cylinder type structure made of Cylinder protein subunits with a lid protein Exists in the cytoplasm Protein folding pathways diffuse Protein into the interior of the proteaosome proteaosome Correctly fold protein Misfolded protein Requires energy - ATP Proteolic enzymes Two options (see figure) Protein folds- correctly Protein released released Does not fold correctly Does destroyed destroyed Destroyed protein The Proteasome (p 359) point of no return How does a protein know to go to the proteasome ? Ubiquitin Ubiquitin Covalent modification of proteins Covalent with ubiquitin marks them for degradation by the proteosome degradation Acts as a tag that target Acts misfolded protein to a proteasome proteasome Attaches to Lysine side chains Reversible MBOC 6­87 Over all Process Creation of a Functional Protein Creation ...
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This note was uploaded on 04/20/2010 for the course BIOL 4064 taught by Professor Dr.reyna during the Spring '09 term at Ouachita Baptist.

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