1 research outputs found
Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe
A transcriptional
regulatory system called heat shock
response
(HSR) has been developed in eukaryotic cells to maintain proteome
homeostasis under various stresses. Heat shock factor-1 (Hsf1) plays
a central role in HSR, mainly by upregulating molecular chaperones
as a transcription factor. Hsf1 forms a complex with chaperones and
exists as a monomer in the resting state under normal conditions.
However, upon heat shock, Hsf1 is activated by oligomerization. Thus,
oligomerization of Hsf1 is considered an important step in HSR. However,
the lack of information about Hsf1 monomer structure in the resting
state, as well as the structural change via oligomerization at heat
response, impeded the understanding of the thermosensing mechanism
through oligomerization. In this study, we applied solution biophysical
methods, including fluorescence spectroscopy, nuclear magnetic resonance,
and circular dichroism spectroscopy, to investigate the heat-induced
conformational transition mechanism of Hsf1 leading to oligomerization.
Our study showed that Hsf1 forms an inactive closed conformation mediated
by intramolecular contact between leucine zippers (LZs), in which
the intermolecular contact between the LZs for oligomerization is
prevented. As the temperature increases, Hsf1 changes to an open conformation,
where the intramolecular LZ interaction is dissolved so that the LZs
can form intermolecular contacts to form oligomers in the active form.
Furthermore, since the interaction sites with molecular chaperones
and nuclear transporters are also expected to be exposed in the open
conformation, the conformational change to the open state can lead
to understanding the regulation of Hsf1-mediated stress response through
interaction with multiple cellular components