Q Why is it in News ?
A Chaperones are a functionally related group of proteins assisting protein folding in the cell under physiological and stress conditions.
Q What are Chaperones?
A
- DNA is a linear chain of nucleotides, portions of which are faithfully transcribed into linear messenger RNA.
- The message in this RNA is translated into strings of amino acids – proteins.
- Proteins need to take a precise three-dimensional shape to become functional entities.
- This protein folding does not happen all by itself, at least most of the time.
- A special bunch of proteins called molecular chaperones assist in correctly folding the protein.
Q What are functions of chaperone proteins ?
A
- In biological systems, Chaperones play crucial roles.
- Many molecular chaperones belong to the class of “heat shock” proteins (or stress-response proteins).
- This is because whenever an organism is subjected to elevated temperatures – a heat shock – proteins in the system begin to lose their native shapes, and chaperones are produced in large quantities to restore order.
Q What is general need of chaperones ?
A Chaperones are needed under physiological conditions too, for normal cellular function since misfolding of proteins can cause a number of diseases.
- Alpha-synuclein protein, present in neurons, is wrongly folded in Parkinson’s disease.
- Brains of Alzheimer’s patients have plaques formed from aggregates of amyloid beta-peptide.
- This accumulation of amyloid fibrils is toxic, leading to widespread destruction of neurons – a ‘neurodegenerative’ disorder.
- Aberrant folding of crystallins of the eye lens leads to cataracts.
Q What are various types of Chaperones ?
A
- Major chaperones in humans include HSP70, HSC70 and HSP90: the numbers express the size of the proteins in kilodaltons.
- In normal cells 1%–2% of all proteins present are heat shock proteins.
- This number rises threefold during stressful conditions.
HSC70: The molecular thermometer
- HSC70 appears to be more like a molecular thermometer, with an ability to sense cold temperatures.
- It is induced by heat, whereas HSC70 is always present at high levels in normal cells.
- This knowledge comes from the study of an intriguing set of disorders, exemplified by Familial Cold Autoinflammatory Syndrome (FCAS).
HSC70 and HSP90: Role in Cancer
- Cancer cells divide at a break-neck pace, and heat shock proteins are very important in maintaining the stressful cancerous state.
- An overabundance of heat shock proteins in cancer cells is an indicator of a poor prognosis. Cancerous cells accumulate mutations in proteins that would normally suppress tumours.
- HSP70 and HSP90 play the roles of villains, as they continue to fold the mutated proteins, thus allowing tumor progression.
