post-translational modification

its modification in protein after its formation in translation.

1. Post-translational Modification Changes in P olypeptide C hains

2. Translation Translation is the synthesis of protein from an mRNA template. This process involves several key molecules including: 1 . mRNA 2 . Ribosome 3 . tRNA 4 . Release Factor

3. Changes after Translation 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.) Changes in the Hydrogen bond proclivity which results in secondary and tertiary structures

4. PTMs The chemical modification of a protein after its translation is known as Post-Translational Modification. They regulate activity, localization and interaction with other cellular molecules such as proteins, nucleic acids, lipids and cofactors.

5. PTMs Amino-Terminal and Carboxyl-Terminal Modifications Loss of Signal Sequences Modification of Individual Amino acids Attachment of Carbohydrate Side Chains Proteolytic Processing Formation of Disulfide Cross-Links

6. Types of PTMs Trimming Covalent Modification Ubiquitination

7. Trimming Removal of a part of the translated sequence. Proteases Protein activation. Portions of the protein chain must be removed by specialized endoproteases . Some precursor proteins are cleaved in the endoplasmic reticulum or the Golgi apparatus; others are cleaved in developing secretory vesicles.

8. P hosphorylation Addition of phosphate group to a protein. It occurs on the hydroxyl groups of serine, threonine, less frequently, tyrosine residues in a protein. The phosphorylation may increase or decrease the functional activity of the protein. Protein kinases ATP + protein phosphoprotein + ADP

9. Examples

10. Glycosylation Addition of glycosyl group or carbohydrate group to a protein. Glycosylation is also used to target proteins to the matrix of lysosomes. It is built sequentially on the hydroxyl groups of serine, threonine, or hydroxylysine (O-linked). N-glycosylation occurs in the endoplasmic reticulum and O- glycosyation in the Golgi.

11. Examples

12. Classes of glycan N-Linked glycans – attached to nitrogen of Asparagine or arginine side chains . O-Linked glycans – attached to hydroxy oxygen of serine,threonine Phospho glycans – linked through the phosphate of serine. C-Linked glycans – Rare form, Sugar is added to a carbon on tryptophan side chain.

13. Protein Folding Proteins must fold to assume their functional, native state. Folding can be spontaneous (as a result of the primary structure) or facilitated by proteins known as chaperones . Foldings of AA give protein a structure.

14. Protein degradation Ubiquintation Ubiquitin is a small regulatory protein that can be attached to the proteins and label them for destruction. Proteins that are defective (for example, misfolded ) are often marked for destruction by ubiquitination Effects in cell cycle regulation, control of proliferation and differentiation, programmed cell death (apoptosis), DNA repair, immune and inflammatory processes and organelle biogenesis.

15. Ubiquitination

16. Importance of PTMs 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 . Play an important part in modifying the end product of expression. Contribute towards biological processes and diseased conditions .

17. Post-translational regulation Once a polypeptide chain is assembled, it still requires two major "finishing steps" before it becomes functional. Chemical modification Folding

18. Chemical modification 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

19. Abundance of collagen The abundance of collagen in the extracellular structures of humans and other mammals makes disorders of collagen deposition. Atherosclerosis-a disease involving stiffening of the arteries, is related to an over-deposition of collagen. Fibrosis-involving hardening of the tissues, is related to excessive collagen synthesis.

20. Progressive Systemic Sclerosis (Scleroderma] A disease of the vascular and immune systems, and a severe connective tissue disorder.