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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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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 |
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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 |
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