p23 and Aha1 - The Networking of Chaperones by Co-chaperones - page 112

Chapter 6
p23 and Aha1

Alexandra Beatrice Rehn and Johannes Buchner

Abstract Hsp90 is a conserved molecular chaperone and is responsible for the fold-
ing and activation of several hundred client proteins, involved in various cellular
processes. The large number and the diversity of these client proteins demand a high
adaptiveness of Hsp90 towards the need of the individual client. This adaptiveness
is amongst others mediated by more than 20 so-called cochaperones that differ in
their actions towards Hsp90. Some of these cochaperones are able to modulate the
ATPase activity of Hsp90 and/or its client protein binding, folding and activation.
p23 and Aha1 are two prominent examples with opposing effects on the ATPase
activity of Hsp90. p23 is able to inhibit the ATP turnover while Aha1 is the strongest
known activator of the ATPase activity of Hsp90. Even though both cochaperones
are conserved from yeast to man and have been studied for years, some Hsp90-
related as well as Hsp90-independent functions are still enigmatic and under current
investigation. In this chapter, we first introduce the ATPase cycle of Hsp90 and then
focus on the two cochaperones integrating them in the Hsp90 cycle.

Keywords Hsp90 ﾷ p23 ﾷ Aha1 ﾷ Hch1

The Hsp90 ATPase Cycle

The molecular chaperone Hsp90 is required for the folding, activation and matu-
ration of several hundred client proteins with diverse cellular functions (McClel-
lan et al. 2007 ; Taipale et al. 2012 ). It is a flexible dimer in which each protomer
consists of an N-terminal- (ND), middle- (MD) and C-terminal domain (CD). The
N-terminal domain, responsible for ATP binding and hydrolysis (Prodromou et al.