2. Proteins are the major components of living
organisms and perform a wide range of essential
functions in cells
Proteins regulate metabolic activity, catalyze
biochemical reactions and maintain structural integrity
of cells and organisms
Proteins
4. Protein Denaturation
The activity of a protein depends on its
three-dimensional structure.
Intramolecular bonds, especially
hydrogen bonds, maintain
the structure.
Hydrogen bonds may break when
the pH drops or the temperature
rises above normal denaturing
the protein
7. Interesting story
F. Ritossa –1960 discovered the heat shock (HS)
response while observing the salivary
cells of Drosophila and named them HSP’s
My name is
Chaperone
8. How do Chaperones work?
One major function of chaperones is to prevent both newly synthesised
polypeptide chains and assembled subunits from aggregating into
nonfunctional structures
High temperatures and other stresses, such as altered pH and oxygen
deprivation, make it more difficult for proteins to form their proper
structures and cause some already structured proteins to unfold
Heat Shock Proteins are induced rapidly at high levels to deal with this
problem
9. Different Types of Heat
Shock Proteins
Heat Shock Proteins are classified by their molecular
weight, size, structure, and function.
They are divided into several families, namely -
1. HSP100
2. HSP90
3. HSP70
4. HSP60 (chaperonin)
5. Small Heat Shock Proteins/ (alpha)-crystalline
proteins
10. HSP100
Functions
-solubilizes protein aggregates thereby dissociating them
-facilitates proteolysis
-essential in yeast for acquired thermotolerance
-essential for yeast prion propagation
6-7 monomer
ATP
no co-chaperon is required
11.
12. HSP 90
stabilizes proteins prior to complete folding or activation
forms stable complexes with inactive glucocorticoid receptor and other
transcription factors
most abundant non-ribosomal protein (cytosolic version)
most abundant protein in endoplasmic reticulum (ER version)
dimer
ATP
HoP and p23
13. HSP90 interacts with HSP40, HSC70/HSP90 organizing protein
(HOP), and co-chaperones to bind and stabilize newly synthesized substrate/client proteins. This ATPregulated
cycle of substrate binding is critical to the activation of many oncogenic signaling molecules.
14. HSP70
monomer
ATP
DnaJ and GrpE
assists in protein transport into mitochondria and the endoplasmic
reticulum
protects proteins under stress
stabilizes proteins prior to complete folding
transports across membranes and proteolysis
15. HSP70 works with HSP40 to capture and transfer misfolded client proteins to prefoldin and other chaperonins for refolding
16. HSP60
14-16 monomer
ATP
GroES and GroEL
mediate the native folding of proteins through
cooperation of HSP70 and 60
17.
18. A) Reconstruction of the GroEL
structure with and without the GroES
™lid∫ from cryoelectron microscopy
pictures.
B) Model of the GroEL chaperone
cycle. Two misfolded proteins (green
and blue) are simultaneously folded
in a phase-shifted manner. The red
circles
symbolize the hydrophobic substrate
binding sites of GroEL
19. sHsp
8-24 monomer
exhibit chaperone activity in vitro and thermoprotection in vivo
produced at significant levels in cells experiencing heat stress
most are heat inducible, but some are synthesized in unstressed
conditions-such as for cell development
20. Denatured or unfolded substrates bind to the hydrophilic surface of small HSP complexes and prevent the
substrate from aggregating.The substrate either stays sequestered or is released to be refolded or degraded.