heat-shock protein
Meaning of heat-shock protein: Molecular chaperones named after the heat experiment that revealed them, though they work constantly and not only in a crisis.
Definition of heat-shock protein
Heat-shock proteins are a family of proteins that help other proteins fold into their correct shape and refold them when stress has pulled them out of shape. They were discovered because cells produce far more of them after a rise in temperature, but the same response follows lack of oxygen, poisons, infection and starvation. Many also work continuously in unstressed cells.
What do they actually do?
A newly made protein emerges as a straight chain and only works once it has folded into a precise three-dimensional shape. Folding can go wrong, and heat, acid or toxins can unravel a shape that was already correct. Unfolded chains expose sticky surfaces normally buried inside, and they clump together into useless aggregates. Heat-shock proteins bind those exposed surfaces, hold the chain apart from its neighbors, and give it a second chance to fold. Where refolding fails they escort the chain to the cell's disposal machinery. The nickname for this role is molecular chaperone.
How are the families named?
| Family | Main role |
|---|---|
| HSP70 | Grips newly made chains as they emerge |
| HSP90 | Finishes and stabilizes signaling proteins and receptors |
| HSP60 | Encloses a chain in a barrel so it can fold undisturbed |
| Small heat-shock proteins | Hold damaged chains in reserve until help arrives |
The numbers are approximate molecular weights in kilodaltons, so the naming records size rather than function.
Why are they studied in disease?
Two lines of interest run in opposite directions. In conditions where proteins misfold and accumulate, more chaperone activity would help. In tumors the reverse applies: cancer cells carry mutated signaling proteins that are unstable and depend on HSP90 to stay folded and active, and they run at a level of internal stress that keeps chaperone protein expression high. Blocking HSP90 would in principle strip several driver proteins at once. Drugs designed to do that have been tested in trials, and none has yet become a standard treatment, largely because the same chaperones are needed by healthy cells.
Also known as
Used in a sentence
Expression of heat-shock protein was elevated in the tumor samples relative to adjacent tissue.
Good to know
The name records the experiment that revealed these proteins rather than the limits of their job, since they respond to many stresses and operate in unstressed cells too.