NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP

Mizushima, Ryota; Kim, Ju Yaen; Suetake, Isao; Tanaka, Hiroaki; Takai, Tomoyo; Kamiya, Narutoshi; Takano, Yu; Mishima, Yuichi; Tajima, Shoji; Goto, Yuji; Fukui, Kenji; Lee, Young-Ho

doi:info:doi/10.1371/journal.pone.0098554

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このアイテムへのリンクには次のURLをご利用ください:https://doi.org/10.1371/journal.pone.0098554

このアイテムへのリンクには次のURLをご利用ください:http://hdl.handle.net/11094/71261

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タイトル	NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP
著者	Mizushima, Ryota Mizushima, Ryota
	Kim, Ju Yaen Kim, Ju Yaen
	Suetake, Isao Suetake, Isao
	Tanaka, Hiroaki Tanaka, Hiroaki
	Takai, Tomoyo Takai, Tomoyo
	Kamiya, Narutoshi Kamiya, Narutoshi
	Takano, Yu Takano, Yu
	Mishima, Yuichi Mishima, Yuichi
	Tajima, Shoji Tajima, Shoji
	Goto, Yuji Goto, Yuji
	Fukui, Kenji Fukui, Kenji
	Lee, Young-Ho Lee, Young-Ho
内容	Mizushima R, Kim JY, Suetake I, Tanaka H, Takai T, et al. (2014) NMR Characterization of the Interaction of the Endonuclease Domain of MutL withDivalent Metal Ions and ATP. PLoS ONE 9(6): e98554. doi:10.1371/journal.pone.0098554
抄録	MutL is a multi-domain protein comprising an N-terminal ATPase domain (NTD) and C-terminal dimerization domain (CTD), connected with flexible linker regions, that plays a key role in DNA mismatch repair. To expand understanding of the regulation mechanism underlying MutL endonuclease activity, our NMR-based study investigated interactions between the CTD of MutL, derived from the hyperthermophilic bacterium Aquifex aeolicus (aqMutL-CTD), and putative binding molecules. Chemical shift perturbation analysis with the model structure of aqMutL-CTD and circular dichroism results revealed that tight Zn2+ binding increased thermal stability without changing secondary structures to function at high temperatures. Peak intensity analysis exploiting the paramagnetic relaxation enhancement effect indicated the binding site for Mn2+, which shared binding sites for Zn2+. The coexistence of these two metal ions appears to be important for the function of MutL. Chemical shift perturbation analysis revealed a novel ATP binding site in aqMutL-CTD. A docking simulation incorporating the chemical shift perturbation data provided a putative scheme for the intermolecular interactions between aqMutL-CTD and ATP. We proposed a simple and understandable mechanical model for the regulation of MutL endonuclease activity in MMR based on the relative concentrations of ATP and CTD through ATP binding-regulated interdomain interactions between CTD and NTD.
公開者	PLOS
掲載誌名	PLOS ONE
巻	9
号	6
開始ページ	e98554
刊行年月	2014-06
ISSN	19326203
DOI	info:doi/10.1371/journal.pone.0098554
URL	http://hdl.handle.net/11094/71261
権利情報	© 2014 Mizushima et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
dcmi資源タイプ	text
DCTERMS.bibliographicCitation	PLOS ONE.9(6) P.e98554
DC.title	NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP
DC.creator	Mizushima, Ryota
	Kim, Ju Yaen
	Suetake, Isao
	Tanaka, Hiroaki
	Takai, Tomoyo
	Kamiya, Narutoshi
	Takano, Yu
	Mishima, Yuichi
	Tajima, Shoji
	Goto, Yuji
	Fukui, Kenji
	Lee, Young-Ho
DC.publisher	PLOS
DC.language" scheme="DCTERMS.RFC1766	英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2014-06
DC.identifier	info:doi/10.1371/journal.pone.0098554
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/71261
DC.description	Mizushima R, Kim JY, Suetake I, Tanaka H, Takai T, et al. (2014) NMR Characterization of the Interaction of the Endonuclease Domain of MutL withDivalent Metal Ions and ATP. PLoS ONE 9(6): e98554. doi:10.1371/journal.pone.0098554
DCTERMS.abstract	MutL is a multi-domain protein comprising an N-terminal ATPase domain (NTD) and C-terminal dimerization domain (CTD), connected with flexible linker regions, that plays a key role in DNA mismatch repair. To expand understanding of the regulation mechanism underlying MutL endonuclease activity, our NMR-based study investigated interactions between the CTD of MutL, derived from the hyperthermophilic bacterium Aquifex aeolicus (aqMutL-CTD), and putative binding molecules. Chemical shift perturbation analysis with the model structure of aqMutL-CTD and circular dichroism results revealed that tight Zn2+ binding increased thermal stability without changing secondary structures to function at high temperatures. Peak intensity analysis exploiting the paramagnetic relaxation enhancement effect indicated the binding site for Mn2+, which shared binding sites for Zn2+. The coexistence of these two metal ions appears to be important for the function of MutL. Chemical shift perturbation analysis revealed a novel ATP binding site in aqMutL-CTD. A docking simulation incorporating the chemical shift perturbation data provided a putative scheme for the intermolecular interactions between aqMutL-CTD and ATP. We proposed a simple and understandable mechanical model for the regulation of MutL endonuclease activity in MMR based on the relative concentrations of ATP and CTD through ATP binding-regulated interdomain interactions between CTD and NTD.
DC.rights	© 2014 Mizushima et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
citation_title	NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP
citation_author	Mizushima, Ryota
	Kim, Ju Yaen
	Suetake, Isao
	Tanaka, Hiroaki
	Takai, Tomoyo
	Kamiya, Narutoshi
	Takano, Yu
	Mishima, Yuichi
	Tajima, Shoji
	Goto, Yuji
	Fukui, Kenji
	Lee, Young-Ho
citation_publisher	PLOS
citation_language	英語
citation_date	2014-06
citation_journal_title	PLOS ONE
citation_volume	9
citation_issue	6
citation_firstpage	e98554
citation_issn	19326203
citation_doi	info:doi/10.1371/journal.pone.0098554
citation_public_url	http://hdl.handle.net/11094/71261

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