HEAT SHOCK PROTIENS

- Purvi Shah

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

Structural Levels of ProteinsPrimary Secondary

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

Protein Denaturation with extreme pH or Temp.

Tempenviron

Tempcell

Folded Proteins

Unfolded Proteins Aggregates

Loss of ProteinFunction

Networkfailure

Death

Cell

Interesting storyF. Ritossa –1960 discovered the heat shock (HS) response while observing the salivary cells of Drosophila and named them HSP’s

My name is Chaperone

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

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

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

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

HSP90 interacts with HSP40, HSC70/HSP90 organizing protein(HOP), and co-chaperones to bind and stabilize newly synthesized substrate/client proteins. This ATPregulatedcycle of substrate binding is critical to the activation of many oncogenic signaling molecules.

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

HSP70 works with HSP40 to capture and transfer misfolded client proteins to prefoldin and other chaperonins for refolding

HSP60 14-16 monomer ATP GroES and GroEL mediate the native folding of proteins through cooperation of HSP70 and 60

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

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

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.

Why Don't Heat Shock Proteins Denature?

Better Hydrogen Bonds

Better Hydrophobic Internal Packing

Enhanced Secondary Structure

Helix Dipole Stabilization

Protein denaturation by temperature