POST TRANSLATIONAL MODIFICATION

OF PROTEIN

KRISHNAKUMAR M S
M.SC BIOCHEMISTRY
 INTRODUCTION

 The structural or chemical modification of protein after translation (synthesis) is called

Post Translational Modification (PTM)
 They increase the Proteome diversity
 Increase the stability of protein
 Transport proteins
 Activate or Inactivate proteins
 To degrade unwanted protein
LOCATION

 The Golgi apparatus is a central membrane organelle that functions as the post-
translational modification factory and trafficking hub for proteins and lipids in the cell

 Post-translational modifications (PTMs) mainly occur in the endoplasmic reticulum of the

cell but sometimes continue in the golgi bodies as well.
 TYPES OF
PTM

Trimming by
Covalent Protein
proteolytic Protein folding
attachment degradation
degradation
 
TRIMMING Many proteins are synthesized as precursors
which are much bigger in size than the functional
proteins.
 Takes place every where inside the cell like
endoplasmic reticulum, golgi bodies etc.
 Some portions of the precursor molecules are
removed by proteolysis to liberate active proteins.
This is called trimming.
 Cleavage of peptide bonds by Endo Proteases
 Activate large in activate
Eg: Pepsinogen(in active)  Pepsin(active)
Preproinsulin (in active) Pro Insulin 
Insulin
(active)
 COVALENT MODIFICATION
 The proteins synthesized in translation are subjected to many covalent changes. By these modification in amino acids,
protein may be converted to active or inactive form.
 Covalent modification refers to the addition or transfer of polypeptide chain that acts as an acceptor region
 It includes
1. Phosphorylation
2. Glycosylation
3. Sulphation
4. Methylation
5. Hydroxylation
Phosphorylation

 Phosphorylation refers to the addition of

phosphate group to the specific residues on
protein ; especially serine ,threonine and
tyrosine residues.
 Protein phosphorylation is brought about by a
special enzyme called protein kinases.
 Phosphorylation is the removal of phosphate
group of the ATP and adding it to the OH group
of the hydroxyl containing amino acids.
 Phosphorylation is mainly used in cell cycle ,cell
signalling and transduction of hormones
 Has a vital role in the cellular process such as
replication ,transcription disruption in
phosphorylation can lead to cancer, Alzheimer’s
diseases, Parkinson diseases and heart diseases .
Glycosylation
 Glycosylation refers to the enzymatic process of addition of oligosaccharide chains to the protein.
 Glycosylation is carried out either in the endoplasmic reticulum or the golgi apparatus and accordingly they
are either N-linked or O-linked glycosylation.
 N-linked glycosylation is so called because the glycan group is attached to the nitrogen atom of asparagine
or arginine whereas, in O-linked glycosylation, the glycan group is attached to the oxygen atom of serine,
threonine or tyrosine.
 Glycosylation not only affects protein folding, but also assists in protein trafficking. Glycosylation usually
tends to solubilize a protein and also it is via these glycan groups that many proteins interact with each
other, especially the extracellular matrix proteins.
Sulfation
 Sulfate modification takes place by the addition of sulphate molecules and these modifications of proteins
occur at tyrosine residues.
 Tyrosine sulfation is accomplished through the activity of tyrosyl proteinsulfo transferases(TPST) which are
membrane associated enzymes of trans golgi network
 There are two known TPST

TWO
TYPES OF
TPST

TPST 1 TPST 2
 Methylation
 The transfer of 1 Carbon methyl groups to nitrogen or oxygen to amino acid side chains
increases the hydrophobicity of the protein and can neutralize the negative amino acid
charge when bounded to carboxylic acids.
 Methylation is mediated by methyl transferases and S adenosylmethionine (SAM) is the
primary methyl group donor.
 Methylation helps in the epigenetic regulation.
 It causes hydrophobicity to the amino acids which influence in protein folding
Hydroxylation
 The biological process of addition of hydroxyl group to a protein amino acid is called
hydroxylation.
 Protein hydroxylation is a type of PTM that involves the conversion of CH group into
COH group and these hydroxylated amino acids are involved in the regulation of some
important factors.
 Hydroxylation increases the strength of collagen in bones
PROTEIN
DEGRADATION/
UBIQUITINATION:
 Ubiquitin Proteasome Pathway(UPP)
 Tagged with a chain of 5 Ubiquitin
{Cytosolic Globular Non enzymatic
Protein) Molecule.
 Recognized by Proteasome
 Degraded to peptide fragments
 Used to degraded misfolded or
defective protein
PROTEIN FOLDING
 The process by which linear peptide chain forms a functional 3D structure by chaperones
 There are 4 stages of protein folding
o primary structure – linear
o Secondary structure – alpha helix and beta plated sheets
o Tertiary structure – 3D
o Quaternary structure – complex of protein subunits.

 The hydrophobic side chain of amino acid coils inside the exposing the hydrophilic side
outward .
 Misfolded protein causes serious complication.
 Eg : Huntington's disease ,cystic fibrosis.
DETECTION OF PTM
 There are several chemical and biological techniques for detection whether the
modification is occurred or completed.
 Mass spectrometry
 Fluorescent staining
Importance of PTMs
 Post translational modifications of proteins which are not gene implate based can regulate
the protein function and causes change in the protein activity.
 Acetylation regulates many diverse functions including DNA recognition.
 Redox dependent PTMs of protein is emerging as key signalling system.
 Study of cell biology ,proteomics
 Study of various diseases like autoimmune disorders cause by defective proteins.
 It increases the diversity and complexity in the proteome
 Protects the protein against cleavage y proteolytic enzyme by blocking the cleavage sites
REFERENCES

 D .Voet And J.G Voet ,Biochemistry, fourth edition

 Lewin’s GENES ,6th edition
 www.googlescholar.com
 https://nptel.ac.in/courses.
THANK
YOU