Identification of amino acids essential for angulin-1/3 binding of the tricellular tight junction binder, angubindin-1

Kuzu, Taiki; Iwashita, Yumi; Tachibana, Keisuke; Nishino, Itsuki; Niwa, Yuki; Uyeda, Atsuko; Matsuo, Kazuki; Nagahama, Masahiro; Kondoh, Masuo

doi:https://doi.org/10.1002/2211-5463.70113

Identification of amino acids essential for angulin-1/3 binding of the tricellular tight junction binder, angubindin-1

Kuzu, Taiki; Iwashita, Yumi; Tachibana, Keisuke et al.

FEBS Open Bio, 2025

アクセス数:13件（2025-11-18 17:53 集計）

固定URL: https://hdl.handle.net/11094/102959

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タイトル	Identification of amino acids essential for angulin-1/3 binding of the tricellular tight junction binder, angubindin-1
著者	ORCID 0009-0000-3239-0646 0009-0000-3239-0646 Scopus Author ID 57871010600 57871010600 著者名 Kuzu, Taiki
	著者名 Iwashita, Yumi
	NRID 1000030432446 1000030432446 著者名 Tachibana, Keisuke
	著者名 Nishino, Itsuki
	NRID 1000020756077 1000020756077 ORCID 0000-0001-8991-0155 0000-0001-8991-0155 researchmap permalink yuki_niwa yuki_niwa Scopus Author ID 55209082200 55209082200 著者名 Niwa, Yuki
	著者名 Uyeda, Atsuko
	著者名 Matsuo, Kazuki
	NRID 1000040164462 1000040164462 著者名 Nagahama, Masahiro
	NRID 1000050309697 1000050309697 researchmap permalink read0083480 read0083480 Scopus Author ID 26643156500 26643156500 著者名 Kondoh, Masuo
キーワード等	angubindin-1
	angulin-1/LSR
	angulin-3/ILDR2
	tight junction
内容	Kuzu T., Iwashita Y., Tachibana K., et al. Identification of amino acids essential for angulin-1/3 binding of the tricellular tight junction binder, angubindin-1. FEBS Open Bio (2025); https://doi.org/10.1002/2211-5463.70113.
抄録	Tight junctions (TJs) are formed where two or three cells meet and are therefore categorized, respectively, into bicellular TJs (bTJs) and tricellular TJs (tTJs). Angubindin-1 is the first tTJ modulator enhancing intestinal macromolecule permeation via binding to the key tTJ proteins, angulin-1 and angulin-3. It is a fragment (amino acids 421–664) derived from domain IV of Clostridium perfringens iota toxin. Here, we identified critical residues (L562, L598, E638, V640, Y643, K644) of angubindin-1 to be essential for binding to angulins by alanine scanning. Mutants substituting these amino acids with alanine exhibited reduced binding to angulin-expressing cells. Simultaneous substitution of all these amino acids lost binding to angulins and resulted in the loss of tTJ-modulating functions of angubindin-1. These insights highlight crucial residues for the tTJ-modulating activity of angubindin-1, which may hold promise in the design of noninvasive, targeted therapeutics using angubindin-1 as a prototype tTJ modulator to enhance the permeation of drugs.
出版者	John Wiley and Sons Inc
収録物名	FEBS Open Bio
刊行年月	2025-09-10
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102959
eISSN	22115463
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1002/2211-5463.70113
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
権利情報	© 2025 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

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	FEBS Open Bio. 2025
DC.title	Identification of amino acids essential for angulin-1/3 binding of the tricellular tight junction binder, angubindin-1
DC.creator	Kuzu, Taiki
	Iwashita, Yumi
	Tachibana, Keisuke
	Nishino, Itsuki
	Niwa, Yuki
	Uyeda, Atsuko
	Matsuo, Kazuki
	Nagahama, Masahiro
	Kondoh, Masuo
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-09-10
DC.identifier	https://doi.org/10.1002/2211-5463.70113
DC.subject	angubindin-1
	angulin-1/LSR
	angulin-3/ILDR2
	tight junction
DC.description	Kuzu T., Iwashita Y., Tachibana K., et al. Identification of amino acids essential for angulin-1/3 binding of the tricellular tight junction binder, angubindin-1. FEBS Open Bio (2025); https://doi.org/10.1002/2211-5463.70113.
DCTERMS.abstract	Tight junctions (TJs) are formed where two or three cells meet and are therefore categorized, respectively, into bicellular TJs (bTJs) and tricellular TJs (tTJs). Angubindin-1 is the first tTJ modulator enhancing intestinal macromolecule permeation via binding to the key tTJ proteins, angulin-1 and angulin-3. It is a fragment (amino acids 421–664) derived from domain IV of Clostridium perfringens iota toxin. Here, we identified critical residues (L562, L598, E638, V640, Y643, K644) of angubindin-1 to be essential for binding to angulins by alanine scanning. Mutants substituting these amino acids with alanine exhibited reduced binding to angulin-expressing cells. Simultaneous substitution of all these amino acids lost binding to angulins and resulted in the loss of tTJ-modulating functions of angubindin-1. These insights highlight crucial residues for the tTJ-modulating activity of angubindin-1, which may hold promise in the design of noninvasive, targeted therapeutics using angubindin-1 as a prototype tTJ modulator to enhance the permeation of drugs.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.rights	© 2025 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
DC.format	102959
citation_title	Identification of amino acids essential for angulin-1/3 binding of the tricellular tight junction binder, angubindin-1
citation_author	Kuzu, Taiki
	Iwashita, Yumi
	Tachibana, Keisuke
	Nishino, Itsuki
	Niwa, Yuki
	Uyeda, Atsuko
	Matsuo, Kazuki
	Nagahama, Masahiro
	Kondoh, Masuo
citation_publisher	John Wiley and Sons Inc
citation_language	英語
citation_date	2025-09-10
citation_journal_title	FEBS Open Bio
citation_doi	https://doi.org/10.1002/2211-5463.70113
citation_public_url	https://hdl.handle.net/11094/102959

Identification of amino acids essential for angulin-1/3 binding of the tricellular tight junction binder, angubindin-1

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