Molecular chaperones and heat shock proteins !

Chaperones are helper proteins that stop new or damaged proteins from clumping and help them fold. Heat and stress switch many of them on.

Updated 2026-11-01

Key facts

Chaperones bind exposed hydrophobic patches of unfolded proteins, preventing aggregation; they do not carry folding information themselves (sequence decides the fold).
Hsp70 family (cytosolic Hsc70/HSPA8, BiP/GRP78 in the ER) binds chains as they leave the ribosome; cycles of ATP binding and hydrolysis grab and release them.
Chaperonins (Hsp60/Hsp10 in mitochondria, TRiC/CCT in the cytosol) are barrel-shaped chambers where a protein folds in isolation, using ATP.
Hsp90 stabilises and activates client proteins such as steroid receptors and many kinases; Hsp90 inhibitors are studied in cancer.
Heat and other stresses activate HSF1, which raises chaperone production (heat shock response); in the ER, misfolded proteins trigger the unfolded protein response (UPR).

1. Hsp70 with ATP binds weakly; ATP hydrolysis (helped by Hsp40) makes it grip the substrate; exchange of ADP for ATP releases it to try folding again.
2. In the GroEL/GroES model (bacterial Hsp60/Hsp10), the substrate enters the ring, a lid closes over it and the protein folds in a protected cavity for a few seconds.
3. In the ER, BiP, calnexin and calreticulin, and protein disulfide isomerase help folding; proteins that keep failing are pulled back to the cytosol, ubiquitinated and destroyed (ERAD).
4. Unliganded steroid receptors sit with Hsp90 in the cytosol; hormone binding releases Hsp90 and lets the receptor move to the nucleus.
5. Chaperones also help proteins cross membranes (mitochondrial import), assemble complexes and refold after stress.
6. When chaperone and proteasome capacity is exceeded, proteins aggregate: amyloid, Lewy bodies, prion plaques.

Also called: Heat shock proteins (HSP), Chaperonins, Unfolded protein response

Neurodegenerative diseases (Alzheimer, Parkinson, Huntington, prion disease) involve aggregates that escape chaperone control.
Z α1-antitrypsin misfolds and polymerises in the ER of hepatocytes, causing liver disease and a lack of the protein in blood.
Some drugs act as 'pharmacological chaperones', stabilising a mutant protein so that it folds and reaches its destination (used in some lysosomal diseases).

Think of the answer, then tap the question to see it.

Do chaperones determine the final shape of a protein?

No: the amino acid sequence determines the fold; chaperones prevent aggregation and give the protein the chance to fold correctly.

Which energy source drives Hsp70 and chaperonin cycles?

ATP binding and hydrolysis.

Which chaperone holds steroid receptors inactive in the cytosol?

Hsp90; hormone binding releases it so the receptor can enter the nucleus.

What transcription factor drives the heat shock response?

HSF1 (heat shock factor 1), which increases production of chaperones.

What happens to proteins that fail to fold in the ER?

They are retro-translocated to the cytosol, ubiquitinated and degraded by the proteasome (ER-associated degradation).

Educational information, not medical advice. For any symptom, see a health professional.

Sources: PDB-101: Molecule of the Month: Chaperones (RCSB Protein Data Bank (PDB-101), 2026); PDB-101: Molecule of the Month: Hsp90 (RCSB Protein Data Bank (PDB-101), 2026); HSP90AA1: Heat shock protein HSP 90-alpha (human) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.