presentation on post translational modifications of proteins

1. Post
translational
modification of
proteins

2. Introduction
 Posttranslational modifications (PTMs) refer to amino acid side chain
modification in some proteins after their biosynthesis
 These processes have a significant impact on the structure and function of
proteins
 Disruption in PTMs can lead to the dysfunction of vital biological processes and
hence to various diseases.
 PTM can be reversible or irreversible

3. Post translational protein modification

4.  There are more than 400 different types of PTMs affecting many aspects of
protein functions.
 Three main PTMs, based on the dbPTM database, are phosphorylation,
acetylation and ubiquitination
 PTMs are important components in cell signaling, as for example
when prohormones are converted to hormones.

5. Summarized information of major PTMs based on
the dbPTM database

6. PHOSPHORYLATION
 Reversible phosphorylation of proteins involves addition of a phosphate group on
serine, threonine, or tyrosine residues and is one of the important and extensively
studied PTM in both prokaryotes and eukaryotes.
 Several enzymes or signaling proteins are switched ‘on’ or ‘off’ by phosphorylation
or dephosphorylation
 phosphorylation is performed by enzymes called ‘kinases’, while
dephosphorylation is performed by ‘phosphatases’.
 Addition of a phosphate group can convert a previously uncharged pocket of
protein into a negatively charged and hydrophilic protein there by inducing
conformational changes in the protein.

7.  Addition of a phosphate group can convert a previously uncharged pocket of protein into a
negatively charged and hydrophilic protein thereby inducing conformational changes in the
protein.
 Phosphorylation has implications in several cellular processes, including cell cycle, growth,
apoptosis and signal transduction pathways
 One example is the activation of p53, a tumor suppressor protein. p53 is used in cancer
therapeutics and is activated by phosphorylation of its N-terminal by several kinases.

8. signaling proteins are switched ‘on’ or ‘off’ by
phosphorylation or dephosphorylation

9. ACETYLATION
 Acetylation is catalyzed via lysine acetyltransferase (KAT) and histone acetyltransferase (HAT)
enzymes.
 The atom to which the acetyl group is attached is usually denoted in the name of either the final
molecule or the enzyme that performs the acetylation.
 Acetylation can occur with thiol groups (sulfur), hydroxyl groups (oxygen), and often amino
groups (nitrogen).
 Acetyltransferases use acetyl CoA as a cofactor for adding an acetyl group (COCH3) to the ε-
amino group of lysine side chains, whereas deacetylases (HDACs) remove an acetyl group on
lysine side chains

11. UBIQUITINATION
 N-terminal ubiquitination involves the addition of a ubiquitin moiety to the free
α-amino group of the first residue of a protein.
 The N-terminal ubiquitin may serve as a target for polyubiquitination, which is a
well-known degradation signal recognized by the 26S proteasome complex.
 The addition of ubiquitin to the N-terminus of a target protein requires the
same enzymatic machinery as ubiquitination of internal residues in the protein
sequence, including ubiquitin activating, conjugating, and ligating enzymes.

12.  There are two enzymes in the ubiquitin pathway, Ube2w and Huwe1, are reported to have the
ability for N-terminal ubiquitination
 Ube2w is an E2 ligase that conjugates ubiquitin to the N-terminal residue of Ataxin-3 and tau
protein
 Huwe1 is the ubiquitin E3 ligase responsible for MyoD N-terminal ubiquitination.
 It was reported to play an important role in the nervous system, including neural progenitor
proliferation, differentiation, cell migration, axon development, and inhibitory neurotransmission

14. THE END