The mitochondrial chaperonin hsp60 is required for its own assembly.
Heatshock protein 60 (hsp60) in the matrix of mitochondria is essential for the folding and assembly of newly imported proteins. Hsp60 belongs to a class of structurally related chaperonins found in organelles of endosymbiotic origin and in the bacterial cytosol. Hsp60 monomers form a complex arranged as two stacked 7-mer rings. This 14-mer complex binds unfolded proteins at its surface, then seems to catalyse their folding in an ATP-dependent process. The question arises as to how such an assembly machinery is itself folded and assembled. Hsp60 subunits are encoded by a nuclear gene and translated in the cytosol as precursors which are translocated into mitochondria and proteolytically processed. In both intact cells and isolated mitochondria of the hsp60-defective yeast mutant mif4, self-assembly of newly imported wild-type subunits is not observed. Functional pre-existing hsp60 complex is required in order to form new, assembled, 14-mer. Subunits imported in vitro are assembled with a surprisingly fast half-time of 5-10 min, indicative of a catalysed reaction. These findings are further evidence that self-assembly may not be the principal mechanism by which proteins attain their functional conformation in the intact cell.
Cheng
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MY
Howard Hughes Medical Institute, Department of Human Genetics, Yale School of Medicine, New Haven, Connecticut 06510.
Hartl
F U
FU
Horwich
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AL
D001692:Biological Transport; D018834:Chaperonin 60; D018833:Chaperonins; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000502:physiology*; D046911:Macromolecular Substances; D008928:Mitochondria / Q000378:metabolism*; D008970:Molecular Weight; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae
D018834:Chaperonin 60; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D011498:Protein Precursors; D011506:Proteins; D018833:Chaperonins