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

Number of Access:1,032（2025-09-29 11:36 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/73658

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Title	Crystal structure of the cis-dimer of nectin-1 : Implications for the architecture of cell-cell junctions
Creator	NRID 1000040598257 1000040598257 CreatorName Narita, Hirotaka
	NRID 1000030467659 1000030467659 CreatorName Yamamoto, Yasunori
	NRID 1000040280507 1000040280507 ORCID 0000-0001-7071-5093 0000-0001-7071-5093 researchmap permalink MamoruSUZUKI MamoruSUZUKI Scopus Author ID 55709928600 55709928600 CreatorName Suzuki, Mamoru
	NRID 1000000634677 1000000634677 CreatorName Miyazaki, Naoyuki
	NRID 1000030749487 1000030749487 CreatorName Yoshida, Asuka
	NRID 1000080534510 1000080534510 CreatorName Kawai, Katsuhisa
	NRID 1000020342751 1000020342751 CreatorName 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 CreatorName Nakagawa, Atushi
	NRID 1000060093514 1000060093514 CreatorName Takai, Yoshimi
	NRID 1000080359843 1000080359843 CreatorName Sakisaka, Toshiaki
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.
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.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	286(14)
Page	12659-12669
Date of Issued	2011-04
Language	English
Handle URL	https://hdl.handle.net/11094/73658
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M110.197368
Relation.isIdenticalTo	PMID 21325282
Access Rights	open access
CopyRight	© the American Society for Biochemistry and Molecular Biology.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	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	English
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	English
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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