The Biology of Molecular Chaperones - Very Complex Activities for Quite Simple Proteins.

GALIGNIANA MD

CURRENT PROTEIN AND PEPTIDE SCIENCE

BENTHAM SCIENCE PUBL LTD

Año: 2014 vol. 15 p. 169 - 170

1389-2037

From a social perspective, the term chaperone refers to a person, usually a matron, who used to accompany young ladies in public and supervise young people at a social gathering to ensure proper behavior. By analogy, proteins that assist others in their proper folding and biological functions are also referred to as chaperones. From the historical perspective, the first recorded use of the term chaperone for a biological phenomenon was in 1976 for a-taipoxin associated proteins [1]. Taipoxin is a potent presynaptic toxin isolated from the venom of an Australian snake named taipan. It is a ternary complex whose subunits (a, b and g) must be properly assembled to potentiate the intrinsic neurotoxic action of the a subunit. In that study, it was postulated that the function of b and g subunits is to sharpening the specificity of action and increasing the stability of the toxic a subunit, like if they were chaperones able to minimize the functional distraction and degradation of the active component. A couple of years later, the term "molecular chaperone" was coined to make reference to the ability of nucleoplasmin to prevent the aggregation of histones with DNA during the assembly of nucleosomes [2]. After this, the name was extended to those proteins that mediate the post-translational assembly of protein complexes. In this regard, it is accepted that some newly translated proteins can fold spontaneously following thermodynamic principles. Nevertheless, most of the proteins are not entirely efficient at folding by following the thermodynamic laws only, and become consequently vulnerable to misfolding processes, a problem which is exacerbated by a highly crowded cellular environment [3]. Although the primarily concept of molecular chaperone was related to its ability to assist the proper folding of newly synthesized peptides in the cytoplasm and refolding of stress-denatured proteins, it should be emphasized that they are also related to a very essential and more sophisticated function, i.e. promoting the correct assembly of oligomeric complexes [4]. Perhaps one the most representative examples for this special feature is the ability of a particular set of molecular chaperones, the heat-shock proteins, to assist the proper assembly of steroid receptor heterocomplexes. In turn, this allows hormone binding to activate the receptor, a ligand-dependent transcription factor [5]. In this sense, the heat-shock protein of 90-kDa, Hsp90, is one of the best examples since its principal role in the cell is to provide biological activity to properly folded client proteins with a preserved tertiary structure acting as a delicate and refined sensor of protein function rather than a gross folding factor. In the above-mentioned example, Hsp90 behaves as a sine qua non factor of the receptor to bind steroid. The term heat-shock protein stems from the original observation that heat-stress greatly enhances the production of this particular class of molecular chaperones. In other words, all heat-shock proteins show properties of molecular chaperones, but not all molecular chaperones must necessarily be heat-shock proteins.