Heat Shock Response

Wolfgang Schumann, University of Bayreuth, Bayreuth, Germany

Published online: April 2001

DOI: 10.1038/npg.els.0000395

In all organisms, a sudden increase in temperature leads to the accumulation of partially unfolded proteins which tend to form life-threatening aggregates within cells. These non-native proteins induce the transiently increased expression of a set of genes termed heat shock genes, and most of their products, designated as heat shock proteins, are involved in either refolding or degradation of the non-native proteins. This reaction is termed the heat shock response

Keywords: molecular chaperones; heat shock response; protease; gene regulation; protein quality control

Figure 1. The DnaK chaperone reaction cycle. The DnaK chaperone system consists of three proteins, DnaK, DnaJ and GrpE, and is involved in the refolding of non-native proteins. (a) The substrate-binding domain of DnaJ binds a partially unfolded protein and transfers it to the DnaK chaperone in its adenosine triphosphate (ATP)-bound form (b). Next, the other domain of DnaJ binds to DnaK to stimulate hydrolysis of ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi), thereby causing closing of the lid (c). Now, the protein starts to refold and, through interaction with GrpE, ADP is released and replaced by ATP, the lid opens, and the protein is released (d). Either the protein is present in its active three-dimensional structure or, if not, it may enter another folding cycle.
Figure 2. The GroE chaperone machine consists of two proteins, GroEL and GroES, and is involved in the refolding of non-native proteins. GroEL forms a double-ring structure with two openings capable of accepting non-native proteins, but not at the same time. (a) A non-native protein has entered the lower ring, each GroEL monomer has one molecule of adenosine triphosphate (ATP) bound and the cavity has been closed by GroES. On the other side, the upper GroEL ring is open and able to accept another non-native protein molecule. (b) This molecule has entered the upper ring, which subseqently binds ATP and is sealed by GroES. At the same time, the lower ring opens and releases its protein (c). Now, the lower ring is able to accept another non-native protein molecule, while the upper rings opens to release its protein into the environment. Under in vitro conditions, a complete folding cycle lasts about 15 s.
Figure 3. Working model for the Clp complex. (a) ClpA and ClpX self-assemble into oligomeric rings in the presence of adenosine triphosphate (ATP), act as molecular chaperones, and accept specific non-native substrate proteins to allow their refolding. (b) Either one or two ClpA or ClpX rings can complex with two proteolytic ClpP rings. Non-native proteins entering the ClpA or ClpX ring are unfolded and transferred to the ClpP rings where their proteolysis into small peptides occurs.
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 Further Reading
    Baumeister W, Walz J, Zühl F and Seemüller E (1998) The proteasome: paradigm of a self-compartmentalizing protease. Cell 92: 367–380.
    book Bukau B (1999) Molecular Chaperones and Folding Catalysts. Amsterdam, The Netherlands: Harwood Academic.
    Bukau B and Horwich AL (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92: 351–366.
    Gottesman S (1999) Regulation by proteolysis: developmental switches. Current Opinion in Microbiology 2: 142–147.
    Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381: 571–580.
    Wickner S, Maurizi MR and Gottesman S (1999) Posttranslational quality control: folding, refolding, and degrading proteins. Science 286: 1888–1893.

Related Sub-Topics:

Protein Folding, Evolution and Degradation | Posttranslational Modification | Protein Degradation
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Article Title: Heat Shock Response
 
How to Cite close
Schumann, Wolfgang(Apr 2001) Heat Shock Response. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000395]