Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity

Tsutsumi, Shinji, Mollapour, Mehdi, Prodromou, Chrisostomos, Lee, Chung-Tien, Panaretou, Barry, Yoshida, Soichiro, Mayer, Matthias P and Neckers, Leonard M (2012) Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity. Proceedings of the National Academy of Sciences, 109 (8). pp. 2937-2942. ISSN 1091-6490

[img] PDF - Published Version
Restricted to SRO admin only

Download (810kB)


Hsp90 is an essential and highly conserved modular molecular
chaperone whose N and middle domains are separated by a
disordered region termed the charged linker. Although its importance
has been previously disregarded, because a minimal linker
length is sufficient for Hsp90 activity, the evolutionary persistence
of extensive charged linkers of divergent sequence in Hsp90
proteins of most eukaryotes remains unexplained. To examine
this question further, we introduced human and plasmodium
native and length-matched artificial linkers into yeast Hsp90. After
evaluating ATPase activity and biophysical characteristics in vitro,
and chaperone function in vivo, we conclude that linker sequence
affects Hsp90 function, cochaperone interaction, and conformation.
We propose that the charged linker, in addition to providing
the flexibility necessary for Hsp90 domain rearrangements—likely
its original purpose—has evolved in eukaryotes to serve as a rheostat
for the Hsp90 chaperone machine

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Biology and Environmental Science
School of Life Sciences > Chemistry
School of Life Sciences > Evolution, Behaviour and Environment
School of Life Sciences > Neuroscience
School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Philippa Erasmus
Date Deposited: 25 Jan 2013 12:45
Last Modified: 08 Mar 2017 07:26

View download statistics for this item

📧 Request an update