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Molecular mechanism of the recognition of bacterially cleaved immunoglobulin by the immune regulatory receptor LILRA2
https://doi.org/10.24517/00067080
https://doi.org/10.24517/000670805d4c8530-0769-4eb8-ac7d-28d68dab4b00
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||||||
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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 | |||||||||
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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× Furukawa, Atsushi× Hirayasu, Kouyuki× Yumoto, Kohei× Fukuhara, Hideo× Arase, Hisashi× Maenaka, Katsumi |
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著者別表示 |
古川, 敦
× 古川, 敦
× 平安, 恒幸
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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 |
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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. | |||||||||
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出版タイプ | VoR | |||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
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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 | |||||||||
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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 | |||||||||
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識別子タイプ | URI | |||||||||
関連識別子 | http://www.asbmb.org/ | |||||||||
関連名称 | http://www.asbmb.org/ |