Cargando…

Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe

[Image: see text] 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 transcriptio...

Descripción completa

Detalles Bibliográficos
Autores principales: Kawagoe, Soichiro, Kumashiro, Munehiro, Mabuchi, Takuya, Kumeta, Hiroyuki, Ishimori, Koichiro, Saio, Tomohide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782367/
https://www.ncbi.nlm.nih.gov/pubmed/36485006
http://dx.doi.org/10.1021/acs.biochem.2c00492
_version_ 1784857325275709440
author Kawagoe, Soichiro
Kumashiro, Munehiro
Mabuchi, Takuya
Kumeta, Hiroyuki
Ishimori, Koichiro
Saio, Tomohide
author_facet Kawagoe, Soichiro
Kumashiro, Munehiro
Mabuchi, Takuya
Kumeta, Hiroyuki
Ishimori, Koichiro
Saio, Tomohide
author_sort Kawagoe, Soichiro
collection PubMed
description [Image: see text] 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.
format Online
Article
Text
id pubmed-9782367
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-97823672022-12-24 Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe Kawagoe, Soichiro Kumashiro, Munehiro Mabuchi, Takuya Kumeta, Hiroyuki Ishimori, Koichiro Saio, Tomohide Biochemistry [Image: see text] 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. American Chemical Society 2022-12-09 2022-12-20 /pmc/articles/PMC9782367/ /pubmed/36485006 http://dx.doi.org/10.1021/acs.biochem.2c00492 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Kawagoe, Soichiro
Kumashiro, Munehiro
Mabuchi, Takuya
Kumeta, Hiroyuki
Ishimori, Koichiro
Saio, Tomohide
Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe
title Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe
title_full Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe
title_fullStr Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe
title_full_unstemmed Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe
title_short Heat-Induced Conformational Transition Mechanism of Heat Shock Factor 1 Investigated by Tryptophan Probe
title_sort heat-induced conformational transition mechanism of heat shock factor 1 investigated by tryptophan probe
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782367/
https://www.ncbi.nlm.nih.gov/pubmed/36485006
http://dx.doi.org/10.1021/acs.biochem.2c00492
work_keys_str_mv AT kawagoesoichiro heatinducedconformationaltransitionmechanismofheatshockfactor1investigatedbytryptophanprobe
AT kumashiromunehiro heatinducedconformationaltransitionmechanismofheatshockfactor1investigatedbytryptophanprobe
AT mabuchitakuya heatinducedconformationaltransitionmechanismofheatshockfactor1investigatedbytryptophanprobe
AT kumetahiroyuki heatinducedconformationaltransitionmechanismofheatshockfactor1investigatedbytryptophanprobe
AT ishimorikoichiro heatinducedconformationaltransitionmechanismofheatshockfactor1investigatedbytryptophanprobe
AT saiotomohide heatinducedconformationaltransitionmechanismofheatshockfactor1investigatedbytryptophanprobe