Molecular chaperones facilitate the correct folding of
other proteins under physiological and stress conditions.
Recently it has become evident that various co-chaperone
proteins regulate the cellular functions of these
chaperones, particularly Hsp70 and Hsp90. Hop is one of
the most extensively studied co-chaperones that is able
to directly associate with both Hsp70 and Hsp90. The
current dogma proposes that Hop functions primarily as
an adaptor that directs Hsp90 to Hsp70-client protein
complexes in the cytoplasm. However, recent evidence
suggests that Hop can also modulate the chaperone
activities of these Hsps, and that it is not dedicated to
Hsp70 and Hsp90. While the co-chaperone function of
Hop within the cytoplasm has been extensively studied,
its association with nuclear complexes and prion proteins
remains to be elucidated. This article will review the
structural features of Hop, and the evidence that its
biological function is considerably broader than previously
envisaged.