Post Translational Modification

Post Translational Modification

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  Post Translational Modifications ofProteins By Lubna Khayal MB-(B)U/17 Microbiology Shaheed Benazir Bhutto Women University
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  Introduction • It isthe chemical modification of protein after its translation. • Key role in functional Proteomics. • They regulate activity, localization and interaction with other cellular molecules such as proteins, nucleic acids, lipids and cofactors.
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  Types of PostTranslational Modifications of Proteins Phosphorylation Glycosylation Ubiquitination S-Nitrosylation Methylation N-Acetylation Lipidation Proteolysis
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  Phosphorylation • Addition ofphosphate group to a protein. • Principally on serine, threonine or tyrosine residues. • Also known as Phosphoregulation. • Critical role in cell cycle, growth, apoptosis and signal transduction pathways.  Protein kinases ATP + protein ———————> phosphoprotein + ADP
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  Glycosylation • The covalentattachment of oligosaccharides • Addition of glycosyl group or carbohydrate group to a protein. • Principally on Asparagine, hydroxylysine, serine or threonine. • Significant effect on protein folding, conformation, distribution, stability and activity.
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  Classes of Glycans •N-Linked glycans – attached to nitrogen of Asparagine or arginine side chains. • O-Linked glycans – attached to hydroxy oxygen of serine,threonine • Phosphoglycans – linked through the phosphate of serine. • C-Linked glycans – Rare form, Sugar is added to a carbon on tryptophan side chain.
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  Ubiquitination • Ubiquitin isa small regulatory protein that can be attached to the proteins and label them for destruction. • Effects in cell cycle regulation, control of proliferation and differentiation, programmed cell death (apoptosis), DNA repair, immune and inflammatory processes and organelle biogenesis.
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  S-Nitrosylation • Nitrosyl (NO)group is added to the protein. • NO a chemical messanger that reacts with free cysteine residues to form S-nitrothiols. • Used by cells to stabilize proteins, regulate gene expression.
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  Alkylation/Methylation • Addition ofmethyl group to a protein. • Usually at lysine or arginine residues. • Binds on nitrogen and oxygen of proteins • Enzyme for this is methyltransferase • Methylation of lysine residues in histones in DNA is important regulator of chromatin structure.
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  N-Acetylation • Addition ofacetyl group to the nitrogen. • Histones are acetylated on lysine residues in the N- terminal tail as a part of gene regulation. • Involved in regulation of transcription factors, effector proteins, molecular chaperons and cytoskeletal proteins. • Methionine aminopeptidase (MAP) is an enzyme responsible for N-terminal acetylation
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  Lipidation • Lipidation attachmentof a lipid group, such as a fatty acid, covalently to a protein. • In general, lipidation helps in cellular localization and targeting signals, membrane tethering and as mediator of protein-protein interactions.
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  Types of lipidation •C-terminal glycosyl phosphatidylinositol (GPI) anchor • N-terminal myristylation • S-palmitoylation • S-prenylation
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  Proteolysis • Cleavage ofpeptide bonds by proteases. • Examples of Proteases- Serine Proteases, Cysteine Proteases, Aspartic acid Proteases. • Involved in Antigen processing, Apoptosis, Cell signaling