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J Biol Chem, Vol. 273, Issue 6, 3679-3686, February 6, 1998
From the Hop is a 60-kDa protein characterized by its
ability to bind the two chaperones, hsp70 and hsp90. We have tested the
function of Hop using an assay for the refolding of denatured firefly
luciferase. We show that Hop is involved in the process of refolding
thermally denatured firefly luciferase in rabbit reticulocyte lysate.
Hop also stimulates refolding by hsp70 and Ydj-1 in a purified
refolding system. Hsp90 can also stimulate refolding, and optimal
refolding is observed in the presence of both Hop and hsp90. Similar
stimulation was observed when Hop was replaced by its yeast homolog
Sti1. In assays of the binding of Hop to hsp70 and hsp90, Hop
preferentially forms a complex with ADP-bound hsp70, and this process
is unaffected by the presence of hsp90. Hop does not alter the ATPase
activity or the rate of ADP dissociation of hsp70. Hop also appears to bind to the ADP-bound form of hsp90, blocking the
ATP-dependent conversion of hsp90 to a form capable of
interacting with p23. Conversely, once p23 is bound to hsp90, Hop
binding is diminished. These results confirm that Hop provides a
physical link between hsp70 and hsp90 and also indicate that Hop
modulates the activities of both of these chaperone proteins.
Hop Modulates hsp70/hsp90 Interactions in Protein Folding
,
, and
Department of Biochemistry and Molecular
Biology, Mayo Graduate School, Rochester, Minnesota 55905 and the
§ Department of Genetics and Howard Hughes Medical
Institute, Yale University School of Medicine,
New Haven, Connecticut 06510
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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