Disordered Motifs and Domains in Cell Control
Poster Session I
7-POS Board 7
How Do Intrinsically Disordered Chaperones Work?
Ohad Suss
1
, Rosi Gilin
1
, Hadar Refaely
2
, Assaf Friedler
2
,
Dana Reichmann
1
.
1
Hebrew University of Jerusalem, Jerusalem, Israel,
2
Hebrew University of Jerusalem,
Jerusalem, Israel.
The ability of cells to sustain and recover after stress conditions depends on a well-developed
network of protein chaperones. Recently, a new class of intrinsically disordered (ID) chaperones,
including the redox-regulated chaperone Hsp33, was discovered. This unique class of ATP-
independent chaperones serves as the first line of defense in problematic stress conditions that
cause both broad protein unfolding and inactivation of essential housekeeping chaperones. One
common feature of this class of chaperones is their ability to rapidly convert large parts of their
structure into unfolded protein segments in response to stress conditions. This state of native
disorder seems to be crucial for their role in preventing protein aggregation by binding partially
unfolded clients and releasing them once stress conditions are abolished.
This mode of action raises fundamental questions regarding the role of intrinsic disorder in
chaperones function, regulation and specificity. To address these questions we used a highly
conserved redox-regulated chaperone, Hsp33, as a model protein. The activation of Hsp33 is
triggered by oxidation, which leads to unfolding of ~40% of its structure. To understand a
mechanism of substrate recognition and role of structural plasticity, we, at first, extended
characterization of the Hsp33 chaperones to eukaryotes. In this study, we characterized a novel
eukaryotic homologue of Hsp33 in Trypanosoma Brucei. Silencing of this chaperone leads to
increase in sensitivity to heat and oxidative conditions in the Trypanosoma parasites. In addition,
to define a role of sequence specificity in chaperone activity, we designed a chimera Hsp33
chaperone by replacing a large region of its binding site by a non-related sequence originated
from a non-Hsp33 protein. Remarkably, the chimera protein exhibited a significant chaperone
activity. This finding challenges the current consensus that function relates directly to protein
sequence, but rather to its structural elements.
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