Chaperones

OLIA NAJON TUSON (15136032)

ROMI MARINA GEORGE (14236008)

SHAHREEN HAMID (14236010 )

INTRODUCTION

 The proteins are macromolecules that execute almost all the activities of the
cells and the responsibles that all of this occur in the normal way.
 The molecular chaperones are a diverse group of families of proteins that are
requires for the correct folding, transport and degradation of others proteins in
vivo.
 FUNCTION

 This is a large group of unrelated protein families whose role is to stabilize

unfolded proteins, unfold them for translocation across membranes or for
degradation, and/ or to assist in their correct folding and assembly.
 Molecular chaperones interact with unfolded or partially folded protein subunits.
 They do not interact with native proteins, nor do they form part of the final folded
structures.
 They stabilize non-native conformation to correct folding of protein subunits.
 Some chaperones are non-specific, and interact with a wide variety of polypeptide
chains.
 They often couple ATP binding or hydrolysis to the folding process.
 Heat shock (HS) and other protein-
damaging stresses cause protein
misfolding and aggregation, which can be
limited by the heat-shock proteins Hsp90,
Hsp70 and Hsp27. These misfolded
proteins can be rescued by the refolding
activity of Hsp70. Proteins that cannot be
productively refolded are targeted to the
proteasome for degradation. The Hsp90-
binding drug geldanamycin (GA) causes
release of client proteins resulting in
proteasomal degradation.
TYPE OF CHAPERONES

 Chemical chaperones : chemical compounds that stabilize proteins against

thermal denaturation. Examples are DMSO (dimethyl sulfoxide), Glycerol,
TMAO(trimethyl amine N-oxide)
 Pharmacological chaperones : It rescue proteins from proteasome degradation
,stabilize them by binding to specific conformations of receptors . Examples are
cycloporin, Vinblatin , verapamil ,amyloidoses.
 Molecular Chaperons: They assist other proteins to achieve active 3D structure.
 Molecular chaperones
• Molecular chaperones: Assist other proteins to achieve a functionally
active 3D structure and thus prevent the formation of a misfolded or
aggregated structure

• 2 major types of molecular chaperones:

- Hsp60 e.g. GroEL/GroES system
- Hsp70 e.g. DnaK-DnaJ-GrpE system

• Remember hsp70 mainly serves to block aggregation while Hsp60

provide an "isolation chamber" in which individual unfolded proteins
can fold unimpeded. Whereas hsp70 prevents improper folding and
aggregation, hsp60 promotes proper folding.
 The GroEL/GroES system: structure
• GroEL barrel: composed of two dimers stacked on top of each. Each dimer consists
of 7 subunits. Hollow tube as site of protein folding.
• GroES: composed of simple ring of 7 smaller proteins. Protein lid
GroEL/GroES system: cycle
 DnaK-DnaJ-GrpE system: structure
• 2 domain:
N-terminal domain (ATPase binding domain)
C-terminal domain (substrate binding domain)
DnaK-DnaJ-GrpE system: cycle
Chaperones in preventing diseases

 reduces the threat of associated neurodegenerative diseases.

Chaperones in CFTR

 Caused due to mutant protein

 Prolonged interaction of nascent peptide with chaperones
 Mutant protein misfolded
 Chaperones dispose the abnormally folded proteins
 CFTR prevented from insertion into the membrane
Chaperones in Neurodegenerative disease

 Huntington’s disease
 Proteins aggregate due to polyglutamine repeats
 Chaperones localize with aggregated proteins
 Inhibit protein degradation
THANKYOU

Any questions?