Phylogenetic and structural insights into the origin of C-type lectin Mincle in vertebrates

Ito, Taiki; Guenther, Carla; Ishikawa, Eri; Yabuki, Takae; Nagae, Masamichi; Nakatani, Yoichiro; Yamasaki, Sho

doi:https://doi.org/10.1007/s00251-025-01375-x

Phylogenetic and structural insights into the origin of C-type lectin Mincle in vertebrates

Ito, Taiki; Guenther, Carla; Ishikawa, Eri et al.

Immunogenetics, 2025, 77(1), 18

アクセス数:521件（2025-08-16 08:16 集計）

固定URL: https://hdl.handle.net/11094/101010

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タイトル	Phylogenetic and structural insights into the origin of C-type lectin Mincle in vertebrates
著者	著者名 Ito, Taiki
	著者名 Guenther, Carla
	NRID 1000020546478 1000020546478 researchmap permalink eishikawa eishikawa Scopus Author ID 57219186766 57219186766 著者名 Ishikawa, Eri
	著者名 Yabuki, Takae
	NRID 1000060619873 1000060619873 ORCID 0000-0002-5470-3807 0000-0002-5470-3807 researchmap permalink mnagae mnagae Scopus Author ID 23009479400 23009479400 著者名 Nagae, Masamichi
	NRID 1000010847891 1000010847891 ORCID 0000-0001-7604-0242 0000-0001-7604-0242 researchmap permalink nakatani_yoichiro nakatani_yoichiro Scopus Author ID 8534216500 8534216500 著者名 Nakatani, Yoichiro
	NRID 1000040312946 1000040312946 researchmap permalink read0117961 read0117961 Scopus Author ID 57219186899 57219186899 ORCID 0000-0002-5184-6917 0000-0002-5184-6917 著者名 Yamasaki, Sho
キーワード等	C-type lectin receptors
	Crystal structure
	FcRγ
	Ligand specificity
	Molecular phylogenetics
	Vertebrates
内容	The version of record of this article, first published in Immunogenetics, is available online at Publisher’s website: https://doi.org/10.1007/s00251-025-01375-x
抄録	Our bodies are continuously exposed to injurious insults by infection and tissue damage, which are primarily sensed by innate immune receptors to maintain homeostasis. Among such receptors is macrophage-inducible C-type lectin (Mincle, gene symbol CLEC4E), a member of the C-type lectin receptor (CLR) family, which functions as an immune sensor for both pathogens and damaged self. To monitor these injurious stimuli, Mincle recognizes disaccharide-based pathogen-derived glycolipids and monosaccharide-based intracellular metabolites, such as β-glucosylceramide. Mincle is well-conserved among mammals; however, there are questions that remain unclear, such as from which lower vertebrate did it arise and whether the original ligand was self or non-self. Here, we found homologues of Mincle and its signaling subunit Fc receptor γ chain (FcRγ) in lower vertebrates, such as reptiles, amphibians, and fishes. The crystal structure of a Mincle homologue revealed that fish Mincle possesses a narrower sugar-binding pocket than that of mammalian Mincle, and accommodates only monosaccharide moieties. These results suggest that Mincle may have evolved from a self-recognizing receptor, and its sugar-binding pocket widened during evolution, presumably to adapt to disaccharide-based glycolipids derived from life-threatening pathogens.
出版者	Springer Science and Business Media Deutschland GmbH
収録物名	Immunogenetics
巻(号)	77(1)
ページ	18
刊行年月	2025-03-22
言語	英語
ハンドルURL	https://hdl.handle.net/11094/101010
PISSN	00937711
eISSN	14321211
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1007/s00251-025-01375-x
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
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
DCTERMS.bibliographicCitation	Immunogenetics. 2025, 77(1), p. 18
DC.title	Phylogenetic and structural insights into the origin of C-type lectin Mincle in vertebrates
DC.creator	Ito, Taiki
	Guenther, Carla
	Ishikawa, Eri
	Yabuki, Takae
	Nagae, Masamichi
	Nakatani, Yoichiro
	Yamasaki, Sho
DC.publisher	Springer Science and Business Media Deutschland GmbH
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-03-22
DC.identifier	https://doi.org/10.1007/s00251-025-01375-x
DC.subject	C-type lectin receptors
	Crystal structure
	FcRγ
	Ligand specificity
	Molecular phylogenetics
	Vertebrates
DC.description	The version of record of this article, first published in Immunogenetics, is available online at Publisher’s website: https://doi.org/10.1007/s00251-025-01375-x
DCTERMS.abstract	Our bodies are continuously exposed to injurious insults by infection and tissue damage, which are primarily sensed by innate immune receptors to maintain homeostasis. Among such receptors is macrophage-inducible C-type lectin (Mincle, gene symbol CLEC4E), a member of the C-type lectin receptor (CLR) family, which functions as an immune sensor for both pathogens and damaged self. To monitor these injurious stimuli, Mincle recognizes disaccharide-based pathogen-derived glycolipids and monosaccharide-based intracellular metabolites, such as β-glucosylceramide. Mincle is well-conserved among mammals; however, there are questions that remain unclear, such as from which lower vertebrate did it arise and whether the original ligand was self or non-self. Here, we found homologues of Mincle and its signaling subunit Fc receptor γ chain (FcRγ) in lower vertebrates, such as reptiles, amphibians, and fishes. The crystal structure of a Mincle homologue revealed that fish Mincle possesses a narrower sugar-binding pocket than that of mammalian Mincle, and accommodates only monosaccharide moieties. These results suggest that Mincle may have evolved from a self-recognizing receptor, and its sugar-binding pocket widened during evolution, presumably to adapt to disaccharide-based glycolipids derived from life-threatening pathogens.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	101010
citation_title	Phylogenetic and structural insights into the origin of C-type lectin Mincle in vertebrates
citation_author	Ito, Taiki
	Guenther, Carla
	Ishikawa, Eri
	Yabuki, Takae
	Nagae, Masamichi
	Nakatani, Yoichiro
	Yamasaki, Sho
citation_publisher	Springer Science and Business Media Deutschland GmbH
citation_language	英語
citation_date	2025-03-22
citation_journal_title	Immunogenetics
citation_volume	77
citation_issue	1
citation_firstpage	18
citation_doi	https://doi.org/10.1007/s00251-025-01375-x
citation_public_url	https://hdl.handle.net/11094/101010

Phylogenetic and structural insights into the origin of C-type lectin Mincle in vertebrates

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