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Protein Biosynthesis -2 By Amr S. Moustafa, M.D.; Ph.D.
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Polyribosome (Polysomes) Several ribosomes and one mRNA
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Protein Targeting Free Vs attached ribosomes Localization signals
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Regulation of Translation The dephosphorylated eIF: Active form Heme prevents eIF phosphorylation Heme stimulates translation Proteins/mRNA interactions: e.g., Ferritin and transferrin receptor synthesis
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Posttranslational Modifications Trimming Covalent modifications: PhosphorylationBiotinylation GlycosylationFarnesylation HydroxylationAcetylation Carboxylation Ubiquitination
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Posttranslational Modifications: Trimming Removal of a part of the translated sequence Proteases protein activation Cellular site of cleavage: ER and Golgi apparatus Secretory vesicles: e.g., insulin After secretion: e.g., collagen At sites of action: zymogen e.g., trypsinogen
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Posttranslational Modifications: Phosphorylation Addition of phosphate to hydroxyl group of Serine and threonine Tyrosine Reversible: Addition by kinases Removal by phosphatases Increase or decrease the activity of a specific protein e.g., Glycogen synthase and glycogen phosphorylase
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Posttranslational Modifications: Phosphorylation
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Posttranslational Modifications: Glycosylation Modifications of : proteins of plasma membrane proteins of lysosome secretory proteins Addition of carbohydrate chains to: Hydroxyl group of serine or threonine (O-linked) Amide group of asparagine (N-linked) Site: Golgi apparatus and ER Protein targeting: e.g., mannose-6-phosphate to lysosomal enzymes
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Posttranslational Modifications: Glycosylation
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Posttranslational Modifications: Hydroxylation Proline and lysine Endoplasmic reticulum Prolyl or lysyl hydroxylases e.g., Collagen
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Posttranslational Modifications: Other Covalent Alterations - 1 Carboxylation: γ-carboxylation of glutamic acid residue for maturation of vitamin K-dependent clotting factors II, VII, IX and X
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Carboxylation
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Posttranslational Modifications: Other Covalent Alterations - 2 Biotinylation Farnesylation e.g., Acetyl Co-A Carboxylase e.g., Protein anchoring to membranes
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Posttranslational Modifications: Ubiquitination Proteins: Defective Rapid turnover Ubiquitin: Small, highly conserved protein Proteasome: Complex proteolytic system ATP-dependent Cytosol
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