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  1. C. 医薬保健学域; 医学類・薬学類・医薬科学類・保健学類
  2. c 10. 学術雑誌掲載論文(医・保健)
  3. 2.査読済論文(薬)

Molecular mechanism of the recognition of bacterially cleaved immunoglobulin by the immune regulatory receptor LILRA2

https://doi.org/10.24517/00067080
https://doi.org/10.24517/00067080
5d4c8530-0769-4eb8-ac7d-28d68dab4b00
名前 / ファイル ライセンス アクション
PH-PR-FURUKAWA-A-295-9531.pdf PH-PR-FURUKAWA-A-295-9531.pdf (1.5 MB)
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Item type 学術雑誌論文 / Journal Article(1)
公開日 2022-09-12
タイトル
タイトル Molecular mechanism of the recognition of bacterially cleaved immunoglobulin by the immune regulatory receptor LILRA2
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
ID登録
ID登録 10.24517/00067080
ID登録タイプ JaLC
著者 Yamazaki, Rika

× Yamazaki, Rika

WEKO 106971

Yamazaki, Rika

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Furukawa, Atsushi

× Furukawa, Atsushi

WEKO 106943
e-Rad 30727699

Furukawa, Atsushi

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Hirayasu, Kouyuki

× Hirayasu, Kouyuki

WEKO 87686
e-Rad 30585170

Hirayasu, Kouyuki

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Yumoto, Kohei

× Yumoto, Kohei

WEKO 106979

Yumoto, Kohei

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Fukuhara, Hideo

× Fukuhara, Hideo

WEKO 106980

Fukuhara, Hideo

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Arase, Hisashi

× Arase, Hisashi

WEKO 106953

Arase, Hisashi

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Maenaka, Katsumi

× Maenaka, Katsumi

WEKO 106954

Maenaka, Katsumi

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著者別表示 古川, 敦

× 古川, 敦

古川, 敦

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平安, 恒幸

× 平安, 恒幸

平安, 恒幸

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提供者所属
内容記述タイプ Other
内容記述 金沢大学医薬保健研究域薬学系
書誌情報 Journal of Biological Chemistry

巻 295, 号 28, p. 9531-9541, 発行日 2020-07-10
ISSN
収録物識別子タイプ ISSN
収録物識別子 0021-9258
ISSN
収録物識別子タイプ ISSN
収録物識別子 1083-351X
NCID
収録物識別子タイプ NCID
収録物識別子 AA00251083
DOI
関連タイプ isIdenticalTo
識別子タイプ DOI
関連識別子 10.1074/jbc.ra120.013354
出版者
出版者 American Society for Biochemistry and Molecular Biology Inc.
抄録
内容記述タイプ Abstract
内容記述 Human leukocyte immunoglobulin-like receptors (LILRs) typically regulate immune activation by binding to the human leukocyte antigen class I molecules. LILRA2, a member of the LILR family, was recently reported to bind to other unique ligands, the bacterially degraded Igs (N-truncated Igs), for the activation of immune cells. Therefore, LILRA2 is currently attracting significant attention as a novel innate immune receptor. However, the detailed recognition mechanisms required for this interaction remain unclear. In this study, using several biophysical techniques, we uncovered the molecular mechanism of N-truncated Ig recognition by LILRA2. Surface plasmon resonance analysis disclosed that LILRA2 specifically binds to N-truncated Ig with weak affinity (Kd = 4.8 mM) and fast kinetics. However, immobilized LILRA2 exhibited a significantly enhanced interaction with N-truncated Ig due to avidity effects. This suggests that cell surface-bound LILRA2 rapidly monitors and identifies bi- or multivalent abnormal N-truncated Igs through specific cross-linking to induce immune activation. Van't Hoff analysis revealed that this interaction is enthalpy-driven, with a small entropy loss, and results from differential scanning calorimetry indicated the instability of the putative LILRA2-binding site, the Fab region of the N-truncated Ig. Atomic force microscopy revealed that N truncation does not cause significant structural changes in Ig. Furthermore, mutagenesis analysis identified the hydrophobic region of LILRA2 domain 2 as the N-truncated Ig-binding site, representing a novel ligand-binding site for the LILR family. These results provide detailed insights into the molecular regulation of LILR-mediated immune responses targeting ligands that have been modified by bacteria. © 2020 Yamazaki et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
権利
権利情報 Copyright © 2020 Yamazaki et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
権利
権利情報 This is an Open Access article under the CC BY license.
著者版フラグ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
関連URI
識別子タイプ URI
関連識別子 https://www.sciencedirect.com/science/article/pii/S002192581748971X?via%3Dihub
関連名称 https://www.sciencedirect.com/science/article/pii/S002192581748971X?via%3Dihub
関連URI
識別子タイプ URI
関連識別子 https://www.journals.elsevier.com/journal-of-biological-chemistry
関連名称 https://www.journals.elsevier.com/journal-of-biological-chemistry
関連URI
識別子タイプ URI
関連識別子 http://www.asbmb.org/
関連名称 http://www.asbmb.org/
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