Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions

Narita, Hirotaka; Yamamoto, Yasunori; Suzuki, Mamoru; Miyazaki, Naoyuki; Yoshida, Asuka; Kawai, Katsuhisa; Iwasaki, Kenji; Nakagawa, Atushi; Takai, Yoshimi; Sakisaka, Toshiaki

doi:https://doi.org/10.1074/jbc.M110.197368

Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions

Narita, Hirotaka; Yamamoto, Yasunori; Suzuki, Mamoru et al.

Journal of Biological Chemistry, 2011, 286(14), 12659-12669

アクセス数:996件（2025-07-15 05:04 集計）

固定URL: https://hdl.handle.net/11094/73658

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タイトル	Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions
著者	NRID 1000040598257 1000040598257 著者名 Narita, Hirotaka
	NRID 1000030467659 1000030467659 著者名 Yamamoto, Yasunori
	NRID 1000040280507 1000040280507 ORCID 0000-0001-7071-5093 0000-0001-7071-5093 researchmap permalink MamoruSUZUKI MamoruSUZUKI Scopus Author ID 55709928600 55709928600 著者名 Suzuki, Mamoru
	NRID 1000000634677 1000000634677 著者名 Miyazaki, Naoyuki
	NRID 1000030749487 1000030749487 著者名 Yoshida, Asuka
	NRID 1000080534510 1000080534510 著者名 Kawai, Katsuhisa
	NRID 1000020342751 1000020342751 著者名 Iwasaki, Kenji
	NRID 1000020188890 1000020188890 ORCID 0000-0002-1700-7861 0000-0002-1700-7861 researchmap permalink atsushi_nakagawa atsushi_nakagawa Scopus Author ID 7202934909 7202934909 著者名 Nakagawa, Atushi
	NRID 1000060093514 1000060093514 著者名 Takai, Yoshimi
	NRID 1000080359843 1000080359843 著者名 Sakisaka, Toshiaki
内容	This research was originally published in Journal of Biological Chemistry. Hirotaka Narita, Yasunori Yamamoto, Mamoru Suzuki, Naoyuki Miyazaki, Asuka Yoshida, Katsuhisa Kawai, Kenji Iwasaki, Atsushi Nakagawa, Yoshimi Takai and Toshiaki Sakisaka. Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions. Journal of Biological Chemistry. 2011; 286, 12659-12669. © the American Society for Biochemistry and Molecular Biology.
抄録	In multicellular organisms, cells are interconnected by cell adhesion molecules. Nectins are immunoglobulin (Ig)-like cell adhesion molecules that mediate homotypic and heterotypic cell-cell adhesion, playing key roles in tissue organization. To mediate cell-cell adhesion, nectin molecules dimerize in cis on the surface of the same cell, followed by trans-dimerization of the cis-dimers between the neighboring cells. Previous cell biological studies deduced that the first Ig-like domain of nectin and the second Ig-like domain are involved in trans-dimerization and cis-dimerization, respectively. However, to understand better the steps involved in nectin adhesion, the structural basis for the dimerization of nectin must be determined. In this study, we determined the first crystal structure of the entire extracellular region of nectin-1. In the crystal, nectin-1 formed a V-shaped homophilic dimer through the first Ig-like domain. Structure-based site-directed mutagenesis of the first Ig-like domain identified four essential residues that are involved in the homophilic dimerization. Upon mutating the four residues, nectin-1 significantly decreased cis-dimerization on the surface of cultured cells and abolished the homophilic and heterophilic adhesion activities. These results indicate that, in contrast with the previous notion, our structure represents a cis-dimer. Thus, our findings clearly reveal the structural basis for the cisdimerization of nectins through the first Ig-like domains.
出版者	American Society for Biochemistry and Molecular Biology
収録物名	Journal of Biological Chemistry
巻(号)	286(14)
ページ	12659-12669
刊行年月	2011-04
言語	英語
ハンドルURL	https://hdl.handle.net/11094/73658
eISSN	1083351X
NCID	AA1202441X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1074/jbc.M110.197368
関連情報 (isIdenticalTo)	PMID 21325282
アクセス権	open access
権利情報	© the American Society for Biochemistry and Molecular Biology.
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	Journal of Biological Chemistry. 2011, 286(14), p. 12659-12669
DC.title	Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions
DC.creator	Narita, Hirotaka
	Yamamoto, Yasunori
	Suzuki, Mamoru
	Miyazaki, Naoyuki
	Yoshida, Asuka
	Kawai, Katsuhisa
	Iwasaki, Kenji
	Nakagawa, Atushi
	Takai, Yoshimi
	Sakisaka, Toshiaki
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2011-04
DC.identifier	https://doi.org/10.1074/jbc.M110.197368
DC.description	This research was originally published in Journal of Biological Chemistry. Hirotaka Narita, Yasunori Yamamoto, Mamoru Suzuki, Naoyuki Miyazaki, Asuka Yoshida, Katsuhisa Kawai, Kenji Iwasaki, Atsushi Nakagawa, Yoshimi Takai and Toshiaki Sakisaka. Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions. Journal of Biological Chemistry. 2011; 286, 12659-12669. © the American Society for Biochemistry and Molecular Biology.
DCTERMS.abstract	In multicellular organisms, cells are interconnected by cell adhesion molecules. Nectins are immunoglobulin (Ig)-like cell adhesion molecules that mediate homotypic and heterotypic cell-cell adhesion, playing key roles in tissue organization. To mediate cell-cell adhesion, nectin molecules dimerize in cis on the surface of the same cell, followed by trans-dimerization of the cis-dimers between the neighboring cells. Previous cell biological studies deduced that the first Ig-like domain of nectin and the second Ig-like domain are involved in trans-dimerization and cis-dimerization, respectively. However, to understand better the steps involved in nectin adhesion, the structural basis for the dimerization of nectin must be determined. In this study, we determined the first crystal structure of the entire extracellular region of nectin-1. In the crystal, nectin-1 formed a V-shaped homophilic dimer through the first Ig-like domain. Structure-based site-directed mutagenesis of the first Ig-like domain identified four essential residues that are involved in the homophilic dimerization. Upon mutating the four residues, nectin-1 significantly decreased cis-dimerization on the surface of cultured cells and abolished the homophilic and heterophilic adhesion activities. These results indicate that, in contrast with the previous notion, our structure represents a cis-dimer. Thus, our findings clearly reveal the structural basis for the cisdimerization of nectins through the first Ig-like domains.
DC.rights	© the American Society for Biochemistry and Molecular Biology.
DC.format	73658
citation_title	Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions
citation_author	Narita, Hirotaka
	Yamamoto, Yasunori
	Suzuki, Mamoru
	Miyazaki, Naoyuki
	Yoshida, Asuka
	Kawai, Katsuhisa
	Iwasaki, Kenji
	Nakagawa, Atushi
	Takai, Yoshimi
	Sakisaka, Toshiaki
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	英語
citation_date	2011-04
citation_journal_title	Journal of Biological Chemistry
citation_volume	286
citation_issue	14
citation_firstpage	12659
citation_lastpage	12669
citation_doi	https://doi.org/10.1074/jbc.M110.197368
citation_pmid	21325282
citation_public_url	https://hdl.handle.net/11094/73658

Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions

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