Post-Translational Modifications


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Post-Translational Modifications

  1. 1. 11/13/2012 MOLECUAR BIOLOGY 1
  2. 2.  Translation is the synthesis of protein from an mRNA template. This process involves several key molecules including:1. mRNA2. Ribosome3. tRNA4. Release Factor11/13/2012 MOLECUAR BIOLOGY 2
  3. 3.  Initiation Elongation Termination11/13/2012 MOLECUAR BIOLOGY 3
  4. 4.  Peptide chain undergoes folding Some amino acids might be changed Carbohydrates or lipids can be added Peptide can be activated by addition or removal of some residue (acetate, phosphate, methyl etc.)11/13/2012 MOLECUAR BIOLOGY 4
  5. 5.  Changes in the Hydrogen bond proclivity which results in secondary and tertiary structures Some of the proteins might remain in cytosol while others are transported across the membrane or even imported into cellular organelles (mitochondria or chloroplasts) to accomplish their functions11/13/2012 MOLECUAR BIOLOGY 5
  6. 6.  The chemical modification of a protein after its translation is known as Post-Translational Modification.11/13/2012 MOLECUAR BIOLOGY 6
  7. 7.  Play a crucial role in generating the heterogeneity in proteins. Help in utilizing identical proteins for different cellular functions in different cell types. Regulation of particular protein sequence behavior in most of the eukaryotic organisms.11/13/2012 MOLECUAR BIOLOGY 7
  8. 8.  Play an important part in modifying the end product of expression. Contribute towards biological processes and diseased conditions. Translocation of proteins across biological membranes.11/13/2012 MOLECUAR BIOLOGY 8
  9. 9.  Trimming Covalent Modification Ubiquitination11/13/2012 MOLECUAR BIOLOGY 9
  10. 10.  Removal of a part of the translated sequence. Proteases Protein activation.11/13/2012 MOLECUAR BIOLOGY 10
  11. 11.  Phosphorylation Glycosylation Hydroxylation Carboxylation Biotinylation Acetylation11/13/2012 MOLECUAR BIOLOGY 11
  12. 12.  Methylation Alkylation Glutamylation Lipoylation Sulfation11/13/2012 MOLECUAR BIOLOGY 12
  13. 13.  Phosphorylation  The addition of a phosphate (PO4) group to a protein or a small molecule.  Can occur on Serine, Threonine, Tyrosine.11/13/2012 MOLECUAR BIOLOGY 13
  14. 14.  Glycosylation  The addition of saccharide to a protein or a lipid molecule. N-Linked Glycosylation • Amide nitrogen of Asparagine O-Linked Glycosylation • Hydroxyl oxygen of Serine and Therionine.11/13/2012 MOLECUAR BIOLOGY 14
  15. 15.  Hydroxylation  The addition of hydroxyl group to proline of protein. Carboxylation  The addition of carboxyl group to glutamate.11/13/2012 MOLECUAR BIOLOGY 15
  16. 16.  Biotinylation  The addition of biotin to protein or nucleic acid. Acetylation  The addition of an acetyl group, usually at the N- terminus of the protein.11/13/2012 MOLECUAR BIOLOGY 16
  17. 17.  Methylation  The addition of a methyl group, usually at lysine or arginine residues. Alkylation  The addition of an alkyl group (e.g. methyl, ethyl).11/13/2012 MOLECUAR BIOLOGY 17
  18. 18.  Glutamylation  Covalent linkage of glutamic acid residues to tubulin and some other Lipoylation  The attachment of a lipoate functionality Sulfation The addition of a sulfate group to a tyrosine.11/13/2012 MOLECUAR BIOLOGY 18
  19. 19.  Highly specific degradation of protein can be achieved through the addition of one to several ubiquitin molecules to a target protein. The process is called Ubiquitination.11/13/2012 MOLECUAR BIOLOGY 19
  20. 20.  These are particularly important for the study of heart disease, cancer, neurodegenerative diseases and diabetes. These are key mechanisms to increase proteomic diversity.11/13/2012 MOLECUAR BIOLOGY 20
  21. 21. 11/13/2012 MOLECUAR BIOLOGY 21
  22. 22. 11/13/2012 MOLECUAR BIOLOGY 22
  23. 23.  A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new protein.11/13/2012 MOLECUAR BIOLOGY 23
  24. 24.  In general, antibiotics are biochemically or fungally produced substances that inhibit the growth of other organisms. Most antibiotics, like many pharmaceuticals, block translation in protein synthesis.11/13/2012 MOLECUAR BIOLOGY 24
  25. 25.  These substances are effective because they take advantage of the tremendous complexity involved in the synthesis of proteins.11/13/2012 MOLECUAR BIOLOGY 25
  26. 26.  Puromycin Streptomycin Erythromycin Tetracyclin Penicillin Chloramphenicol Rifampin Fusidic Acid Thiostrepton11/13/2012 MOLECUAR BIOLOGY 26
  27. 27.  Puromycin  Inhibits protein synthesis at translation by prematurely terminating a peptide chain.  In simple terms, the part of puromycin that resembles an aminoacyl end of tRNA can bind to the A site of a ribosome.11/13/2012 MOLECUAR BIOLOGY 27
  28. 28. Streptomycin Depending on its concentration, streptomycin can affect bacterial cells in two ways.Low concentrationAt low concentrations, it induces mRNA misreading, so that improper amino acids are incorporated into the polypeptide.11/13/2012 MOLECUAR BIOLOGY 28
  29. 29.  High concentration At high concentrations, 70s nonproductive ribosome: mRNA complexes accumulate, preventing formation of active initiation complexes with new mRNA.11/13/2012 MOLECUAR BIOLOGY 29
  30. 30.  Once a polypeptide chain is assembled, it still requires two major "finishing steps" before it becomes functional. Chemical modification Folding11/13/2012 MOLECUAR BIOLOGY 30
  31. 31.  Chemical modification involves three steps: modification of amino acid residues into other types, addition of organic units (such as sugars or lipids) to specific amino acids, enzymatic cleavage of one or more amino acids from a region of the polypeptide chain.11/13/2012 MOLECUAR BIOLOGY 31
  32. 32.  The abundance of collagen in the extracellular structures of humans and other mammals makes disorders of collagen deposition. Atherosclerosis Fibrosis Progressive Systemic Sclerosis (Scleroderma)11/13/2012 MOLECUAR BIOLOGY 32
  33. 33.  Atherosclerosis  a disease involving stiffening of the arteries, is related to an over-deposition of collagen  Fibrosis  A disease involving hardening of the tissues, is related to excessive collagen synthesis.11/13/2012 MOLECUAR BIOLOGY 33
  34. 34.  Progressive Systemic Sclerosis (Scleroderma)  A disease of the vascular and immune systems, and a severe connective tissue disorder.11/13/2012 MOLECUAR BIOLOGY 34
  35. 35. 11/13/2012 MOLECUAR BIOLOGY 35