Heat Shock Proteins (HSPs) are a ubiquitous group of molecular chaperone proteins that have evolved unique mechanisms, within their host cells, to facilitate survival in hostile environments such as heat, oxidative (hypoxia), pH and cold. Under permissive conditions, the proteins are constitutively expressed and many have important or essential roles in the cell, including the protein export, regulation, turnover and the prevention of protein aggregation.  There are many classes of HSPs, which are divided into 5 families on the basis of their apparent molecular size and sequence homology:  Hsp100, Hsp90, Hsp70, Hsp60 and the small HSP’s (15-30kDa).

HSP100 proteins are amongst the most conserved within their chaperone family. The most characterised member within this group is the homohexameric toroid protein found in yeast, HSP104. Their major role is thought to be targeting mis-folded proteins and passing them through their central cavity, thus allowing the mis-folded protein to refold.

HSP90 has five isoforms to date including the cytoplasmic HSP90a and HSP90b. The HSP90’s are thought to regulate more than 200 proteins, covering many cellular processes within the cell. The list is constantly being updated however the most characterised so far are: HIF-1a, SRC, HER2, EGFR, BRAF, AKT, MET, VEGFR and FLT3.

Human cells contain several HSP70 family members and play many roles within the cell. Interestingly, they have been found specifically affecting the intrinsic and extrinsic pathway of apoptosis, by inhibiting the apoptotic mediator protein, Bax translocation. Jointly with its co-chaperone HSP40, Hsp70 also blocks TNF-induced apoptosis and HSP70 also directly interacts with Apaf-1, consequently inhibiting the recruitment of procaspase-9 to the apoptosome and the resulting caspase-3 activation.

The HSP60 family of proteins generally comprise of a 7 or 8 sub-units, in a double ringed conformation. The family exhibit ATPase activity and it is thought that the binding and hydrolysis of ATP is essential for the reaction cycle and the result binding and release of partially or mis-folded substrate proteins.

The small HSPs are the most diverse and least studied family and have a low overall identity between fellow members of 20-30% and this is mainly found in the C-terminal half of the proteins. Alpha A Crystallin and Alpha B Crystallin constitute a large percentage of the protein found in the vertebrate eye lenses, function as chaperones by preventing protein aggregation and refolding.