The Heat Shock Response in Bacteria

Proteins denature under heat stress. This denaturation of proteins causes the transcription of heat shock proteins (HSPs) to deal with the problem. The production of HSPs is rapid, and facilitates repair of the damaged cell. If the temperature remains high, heat shock proteins will remain at a steady-state level in the cell, which is higher than the initial, cooler temperature state, but lower than the peak reached when cell repair was active. The cell has a need for several HSPs at all temperatures, but the need is elevated at higher temperatures and results in an increased rate of synthesis.

There are two major classes of heat shock proteins: proteases (Lon) and chaperones (DnaK, DnaJ, GrpE, and GroELS). Proteases degrade proteins that are misfolded (and some normal proteins) while chaperones recognize exposed hydrophobic regions that shouldn’t be exposed, binds to them, and places those proteins in a chamber which allows the proteins to refold properly.

HSPs are grouped into families based on their molecular weight. Proteins with a weight of about 70 kDa are grouped into the Hsp70 family. Those with a molecular weight of 60 kDa are grouped into the Hsp60 family, etc.

Following a temperature upshift (ex: from 30-42 C) there is an increase in the amount of sigma factor 32, or RpoH. This factor is responsible for the synthesis of at least 30 HSPs that work in the cytoplasm. Sigma 32 is not active at lower temperatures, and becomes stable after heat shock. Because of this, sigma 32 is considered a major heat shock regulon. Organsims that don’t make sigma 32 are unable to grow at temperatures above 20 C.

During normal temperatures and growth, sigma 32 is an unstable protein with a half life of 60 seconds. After a heat shock (e.g. 30-42 C) the protein stablizes for a few minutes, and it accumulates in the cytoplasm. At non stress temperatures, cytoplasmic proteins DnaK and DnaJ bind to sigma 32, making it subject to proteolysis by proteases (including Lon). At higher temperatures, DnaK and DnaJ preferantally bind to denatured proteins, leaving sigma 32 unmolested and able to bind to RNAP. This sigma-RNAP complex protects sigma 32, and results in a holoenzyme that transcribes the Hsp sigma 32 regulon. Therefore, it is the amount of denatured protein (as opposed to temperature directly) that results in the transcription of heat shock proteins. (This point is further supported by the transcription of HSPs after other types of damage that cause protein denaturation). During heat shock periods, there is an increase in the transcription of mRNA for sigma 32. After heat stablizes, sigma 32 activity lowers rather than the concentration.

At very high temperature (45-50 C) the sigma E regulon is activated, which protects extracytoplasmic proteins from damage. Very high temperatures can cause proteins in the membrane to misfold, which is the signiling pathway to activate sigma E (or sigma 24) in the cytoplasm. When sigma E is activated it binds to RNAP, and the sigma E regulon (which consists of at least 11 genes) is transcribed. (This mimics the way sigma 32 is controlled and transcribed) These genes code for proteins and proteases that are involved in the folding, refolding, and degredation of misfolded proteins in the cell envelope. At lower temperatures, sigma E is bound by an anti-sigma factor in the inner membrane. Envelope stress allows for the release of sigma E, when then binds to RNAP.

Sigma S is considered the master regulator for general stress response, including heat shock, nutrient stress, etc.

One thought on “The Heat Shock Response in Bacteria”

Leave a Reply