Genetics Lecture Notes PDF

Genetics Post-translational processing LECTURE (8) DR. El-Sawy 0  Genetics Post-translational p...

Genetics Post-translational processing LECTURE (8) DR. El-Sawy 0  Genetics Post-translational processing Types Co-translational modifications Post-translational modifications Changes occur while protein is still Changes occur after protein synthesis attached to ribosome. completed. Definition  The chemical modification of polypeptide or certain amino acid residues of a protein after its synthesis. Site  Endoplasmic Reticulum and Golgi apparatus. Include:  Folding of polypeptide chain to become functioning.  Get secondary, Tertiary and quaternary structure.  Not all proteins fold spontaneously, some proteins need chaperones to fold correctly.  Abnormal or misfolding of proteins cause diseases as A) Protein Alzheimer's disease. Folding DR. El-Sawy 1  Genetics Post-translational processing  Removal of part of the peptide chain.  Conversion of inactive protein to active one.  Examples: B) Trimming Pre-Proinsulin is converted into insulin. Zymogen of GIT e.g. inactive pancreatic trypsinogen become active trypsin.  Proteins may be activated or inactivated by attachment of a variety of chemical groups to their composing amino acids.  Examples: 1. Phosphorylation 2. Hydroxylation 3. Carboxylation 4. Glycosylation C) Covalent Modification DR. El-Sawy 2  Genetics Post-translational processing Phosphorylation Hydroxylation Carboxylation Glycosylation addition Hydroxyl group to Carboxylic group to CHO group to Phosphate group to protein. of protein (Proline) protein (glutamate) protein.  Protein kinases catalyses  Protein hydroxylase  Carboxylase  Glycosylase phosphorylation catalyzes catalyzes catalyzes  Protein phosphatases hydroxylation. carboxylation. glycosylation. catalyses dephosphorylation. Example  Carboxylation of  As in maturation of clotting factors is  Hormones (TSH) collagen required for  Antibodies. coagulation. DR. El-Sawy 0  Genetics Post-translational processing Regulation of translation process :  By control activity of initiation factors (IF-2).  Example : 1. Interferon (anti-viral drug) stimulates IF-2 phosphorylation At level of Initiation → inhibit translation → decrease viral protein synthesis → Stop virus from growing and dividing. 2. Heme ↑ globin synthesis by preventing IF-2 phosphorylation  Diphtheria toxin inhibits elongation factor 2 (EF-2) → inhibit At level of elongation host protein synthesis. Clinical correlates : 1. Mechanism of action of some drugs affects rate of protein synthesis: Interferon stimulates phosphorylation of IF-2, so inhibits translation and decrease viral protein synthesis. Some antibiotics inhibits protein synthesis at different stage in bacteria. 2. Many mechanisms that control protein synthesis explain pathophysiology of some diseases as diphtheria: Diphtheria toxin inhibits EF-2 → inhibits translocation step → inhibition of protein synthesis → cell death DR. El-Sawy 0  Genetics Post-translational processing Protein synthesis in bacteria is a primary target for antibiotics. Antibiotic Target Function Interfering with the initiation step, or Streptomycin 30S misread mRNA block the A site to prevent binding of Tetracycline 30S aminoacyl-tRNA Erythromycin 50S Inhibit the translocation step ribosome of Premature termination Puromycin Prokaryotes and (analogue of aminoacyl-tRNA) Eukaryotes DR. El-Sawy 1