Disordered Motifs and Domains in Cell Control - October 11-15, 2014

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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