Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)

Abstract The zinc transcriptional regulator (ZitR) functions as a metalloregulator that fine tunes transcriptional regulation through zinc-dependent DNA binding. However, the molecular mechanism of zinc-driven allosteric control of the DNA binding to ZitR remains elusive. Here, we performed enhanced...

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Autores principales:	Xinheng He, Duan Ni, Hao Zhang, Xinyi Li, Jian Zhang, Qiang Fu, Yaqin Liu, Shaoyong Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e9c7e58805aa4c4487671a6128fcfc20
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spelling	oai:doaj.org-article:e9c7e58805aa4c4487671a6128fcfc202021-12-02T16:35:41ZZinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)10.1038/s41598-020-70381-82045-2322https://doaj.org/article/e9c7e58805aa4c4487671a6128fcfc202020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70381-8https://doaj.org/toc/2045-2322Abstract The zinc transcriptional regulator (ZitR) functions as a metalloregulator that fine tunes transcriptional regulation through zinc-dependent DNA binding. However, the molecular mechanism of zinc-driven allosteric control of the DNA binding to ZitR remains elusive. Here, we performed enhanced sampling accelerated molecular dynamics simulations to figure out the mechanism, revealing the role of protein dynamics in the zinc-induced allosteric control of DNA binding to ZitR. The results suggest that zinc-free ZitR samples distinct conformational states, only a handful of which are compatible with DNA binding. Remarkably, zinc binding reduces the conformational plasticity of the DNA-binding domain of ZitR, promoting the population shift in the ZitR conformational ensemble towards the DNA binding-competent conformation. Further co-binding of DNA to the zinc–ZitR complex stabilizes this competent conformation. These findings suggest that ZitR–DNA interactions are allosterically regulated in a zinc-mediated conformational preselection manner, highlighting the importance of conformational dynamics in the regulation of transcription factor family.Xinheng HeDuan NiHao ZhangXinyi LiJian ZhangQiang FuYaqin LiuShaoyong LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xinheng He Duan Ni Hao Zhang Xinyi Li Jian Zhang Qiang Fu Yaqin Liu Shaoyong Lu Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)
description	Abstract The zinc transcriptional regulator (ZitR) functions as a metalloregulator that fine tunes transcriptional regulation through zinc-dependent DNA binding. However, the molecular mechanism of zinc-driven allosteric control of the DNA binding to ZitR remains elusive. Here, we performed enhanced sampling accelerated molecular dynamics simulations to figure out the mechanism, revealing the role of protein dynamics in the zinc-induced allosteric control of DNA binding to ZitR. The results suggest that zinc-free ZitR samples distinct conformational states, only a handful of which are compatible with DNA binding. Remarkably, zinc binding reduces the conformational plasticity of the DNA-binding domain of ZitR, promoting the population shift in the ZitR conformational ensemble towards the DNA binding-competent conformation. Further co-binding of DNA to the zinc–ZitR complex stabilizes this competent conformation. These findings suggest that ZitR–DNA interactions are allosterically regulated in a zinc-mediated conformational preselection manner, highlighting the importance of conformational dynamics in the regulation of transcription factor family.
format	article
author	Xinheng He Duan Ni Hao Zhang Xinyi Li Jian Zhang Qiang Fu Yaqin Liu Shaoyong Lu
author_facet	Xinheng He Duan Ni Hao Zhang Xinyi Li Jian Zhang Qiang Fu Yaqin Liu Shaoyong Lu
author_sort	Xinheng He
title	Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)
title_short	Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)
title_full	Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)
title_fullStr	Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)
title_full_unstemmed	Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)
title_sort	zinc-mediated conformational preselection mechanism in the allosteric control of dna binding to the zinc transcriptional regulator (zitr)
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e9c7e58805aa4c4487671a6128fcfc20
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Zinc-mediated conformational preselection mechanism in the allosteric control of DNA binding to the zinc transcriptional regulator (ZitR)

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