The roles of molecular chaperones in vivo.
Table 1 summarizes the families of chaperones mentioned in this review, and lists their proposed functions. Many of these proteins are named in the accompanying review of Burston and Clarke. Molecular chaperones are proteins which interact with other proteins and help them to reach their final, active conformation. They appear to do this by binding them in an unfolded or partially folded state and subsequently releasing them in an altered form. This property may endow them with several essential or important roles in addition to helping newly synthesized proteins to fold correctly, such as repairing damaged proteins and assisting proteins in membrane translocation. To confirm that a given protein has molecular chaperone activity in vivo, it is necessary to show that interactions between the chaperone and other proteins do occur in the cell, and that loss of the molecular chaperone leads to the accumulation of inactive or precursor protein. The hsp70 protein family are highly conserved and ubiquitous. Genetic studies confirm that their depletion leads to the accumulation of inactive precursor or other proteins, and immunochemical studies show they associate with nascent polypeptides. They are implicated not only in protein folding, but also in protein transport across membranes and reactivation of heat-damaged proteins. The hsp60 proteins are also ubiquitous and very similar in sequence. Those found in bacteria and organelles, such as mitochondria (the GroEL family), are essential at all temperatures, and particularly after heat shock. Their loss or depletion leads to the formation of protein aggregates and eventual cell death. A co-chaperone protein (GroES) is required for their function. Cytosolic homologues (the TCP1 family) are also essential, though not heat-shock induced; they are believed to have a chaperone role in tubulin assembly and their actual role in the cell may be much broader. Many other proteins may have a chaperone function in vivo. Such a function may be specific to a particular substrate (such as the PapD protein in E. coli); others may be more general (such as hsp90 and SecB). Evidence is still needed to demonstrate whether all those proteins which show chaperone behaviour in vitro actually have such a role in vivo. It seems likely that different classes of chaperone may overlap in their specificity, and it is certain that the various proteins classed as molecular chaperones fulfil a wide variety of roles in the cell.
Lund
P A
PA
School of Biological Sciences, University of Birmingham, U.K.
D018835:Chaperonin 10 / Q000502:physiology; D018834:Chaperonin 60 / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation
D018835:Chaperonin 10; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones