PRESENTED BY

KAVYA G. PILLAI
ROLL NO:56
1ST MSC ZOOLOGY
 INTRODUCTION

The polypeptide formed at the end of translation

cannot function as a protein.
Therefore , the translation products often undergo a
variety of modifications.
It is known as post translational modifications.
PROTEIN FOLDING
The information required for a protein to adopt its 3-
D conformation is provided by its amino acid
sequence .
The overall folding process is cooperative.
Smaller proteins undergo folding spontaneously by a
self assembly process.
CHAPERONES
The term was 1st used by Ron Laskey and colleagues
to describe nucleoplasmin protein.
Chaperons facilitate proper folding of nascent
proteins.
Chaperones can fold newly made proteins into
functional conformations, refold misfolded or
unfolded proteins into functional conformations ,
dissemble potentially toxic protein aggregates that
Form due to protein misfolding , assemble and
dismantle large multiprotein complexes & mediate
transformations between inactive and active forms of
proteins.
Chaperones which in eukaryotes are located in every
cellular compartment and organelle, bind to the target
proteins also called substrate or client proteins –
whose folding they will assist.
Chaperons use a cycle of ATP binding, ATP
hydrolysis to ADP & exchange of a new ATP
molecule for the ADP to induce a series of
conformational changes that are essential for their
function.
Two general families of chaperones:
Molecular chaperones
Chaperonins
CHAPERONES
The heat shock proteins HSP 70 in the cytosol and its
homologs ( HSP 70 in mitochondrial matrix, BiP in
ER,etc) are molecular chaperones.
They were 1st identified by their rapid appearance after
a cell had been stressed by heat shock.
Mechanism :
When bound to ATP , the monomeric HSP 70 protein
assumes an open conformation, in which an exposed
hydrophobic substrate binding pocket transiently
binds to exposed incompletely folded target protein
and then rapidly releases this substrate, as long as ATP
is bound.
The hydrolysis of bound ATP causes the molecular
chaperone to assume a closed form that binds its
substrate protein much tightly and this tighter binding
appears to facilitate the target proteins folding,
thereby preventing it from aggregating with other
unfolded proteins.
Next the exchange of ATP for the chaperone bound
ADP causes a conformational change in the chaperone
that releases the target protein and regenerates an
“empty”, ATP bound HsP 70 ready to fold another
protein.
 If the target is now properly folded, it cannot bind to
an HsP 70. If it remains atleast partially unfolded, it can
bind again to give a chaperone another chance to help
fold it properly.
Another example for molecular chaperone is HsP 90.
CHAPERONINS
Protein folding is assisted by another class of
proteins, the chaperonins, also called HsP 60.
These huge cylindrical supramolecular assemblies are
formed from two rings of oligomers.
 BIOCHEMICAL MODIFICATIONS
GLYCOSYLATION:
Protein modification by the addition of carbohydrate
is called glycosylation.
These proteins called glycoproteins are usually
secreted or localized to the cell surface.
The carbohydrate moieties of these proteins are
important for protein folding in ER.
Based on the site of attachment of carbohydrate side
chain , glycoproteins are either N-linked or O-linked .
In the former , carbohydrate is attached to the
Nitrogen atom in the side chain of asparagine.
In the latter, sugar is attached to oxygen atom in the side
chain of serine or threonine.
Sugars that are directly attached to these positions are
usually N-acetyl glucosamine or N-acetyl galactosamine
respectively.
ATTACHMENT OF LIPIDS:
3 types of lipid additions –
N-myristoylation-myristic acid,a 14 carbon fatty acid is
attached to an N-terminal glycine residue of some proteins
during translation.
Prenylation-prenyl groups are attached to sulphur atoms in
the side chains of cysteine residue located near C-terminal
Of polypeptide chain.
Palmitoylation-palmitic acid is added to the sulphur
atoms of the side chains of internal cysteine residues.
ATTACHMENT OF GLYCOLIPIDS:
Addition of glycolipids to C-terminal carboxy groups
of proteins and glycolipids act as anchors.
ACYLATION:
Many proteins are modified at N-terminal by
acylation.
In most cases, the initiator methionine is hydrolysed
and an acetyl group is added to new N-terminal amino
acid .
Acetyl co-A is the acetyl donar for these reactions.
METHYLATION:
Addition of methyl group occurs on nitrogen and
oxygen in the polypeptides.
PHOSPHORYLATION:
Transfer of phosphate group from ATP to hydroxyl
group of 3 amino acids (serine, threonine, tyrosine )by
protein kinase .
Dephosphorylation by phosphatase.
SULPHATION:
Sulphate modification of proteins occurs at tyrosine
residues such as in fibrinogen and in some secreted
proteins . Eg ., gastrin.