From UPSC perspective, the following things are important :
Prelims level : Chaperone Protein
Mains level : NA
Chaperones are a functionally related group of proteins assisting protein folding in the cell under physiological and stress conditions.
What are Chaperones?
- 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.
Functions of chaperone proteins
- 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.
General need of chaperones
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.
Types of Chaperones
- 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.