Premium
The human cytosolic molecular chaperones hsp90, hsp70 (hsc70) and hdj‐1 have distinct roles in recognition of a non‐native protein and protein refolding.
Author(s) -
Freeman B. C.,
Morimoto R. I.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00660.x
Subject(s) - biology , chaperone (clinical) , hsp70 , protein folding , biochemistry , cytosol , recombinant dna , heat shock protein , enzyme , gene , medicine , pathology
The properties of molecular chaperones in protein‐assisted refolding were examined in vitro using recombinant human cytosolic chaperones hsp90, hsc70, hsp70 and hdj‐1, and unfolded beta‐galactosidase as the substrate. In the presence of hsp70 (hsc70), hdj‐1 and either ATP or ADP, denatured beta‐galactosidase refolds and forms enzymatically active tetramers. Interactions between hsp90 and non‐native beta‐galactosidase neither lead to refolding nor stimulate hsp70‐ and hdj‐1‐dependent refolding. However, hsp90 in the absence of nucleotide can maintain the non‐native substrate in a ‘folding‐competent’ state which, upon addition of hsp70, hdj‐1 and nucleotide, leads to refolding. The refolding activity of hsp70 and hdj‐1 is effective across a broad range of temperatures from 22 degrees C to 41 degrees C, yet at extremely low (4 degrees C) or high (>41 degrees C) temperatures refolding activity is reversibly inhibited. These results reveal two distinct features of chaperone activity in which a non‐native substrate can be either maintained in a stable folding‐competent state or refolded directly to the native state; first, that the refolding activity itself is temperature sensitive and second, that hsp90, hsp70 (hsc70) and hdj‐1 each have distinct roles in these processes.