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Molecular basis of sugar recognition by collectin-K1 and the effects of mutations associated with 3MC syndrome
https://asahikawa-med.repo.nii.ac.jp/records/5517
https://asahikawa-med.repo.nii.ac.jp/records/551723dbb21c-1659-4b84-b626-97cf47634c02
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
6528.pdf (3.2 MB)
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| Item type | 学術雑誌論文 / Journal Article_02(1) | |||||
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| 公開日 | 2016-08-17 | |||||
| タイトル | ||||||
| タイトル | Molecular basis of sugar recognition by collectin-K1 and the effects of mutations associated with 3MC syndrome | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Complement activation | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | structural biology | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | C-type lectin | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | 3MC syndrome | |||||
| 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 | |||||
| 著者 |
Umakhanth, Venkatraman Girija
× Umakhanth, Venkatraman Girija× Christopher, M Furze× Alexandre, R Gingras× 吉崎, 隆之× 大谷, 克城× Jamie, E Marshall× A, Katrine Wallis× Wilhelm, J Schwaeble× Mohammed, El-Mezgueldi× Daniel, A Mitchell× Peter, CE Moody× 若宮, 伸隆× Russell, Wallis |
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| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 値 | Yoshizaki, Takayuki | |||||
| 著者 ローマ字 | ||||||
| 値 | Ohtani, Katsuki | |||||
| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 著者 ローマ字 | ||||||
| 値 | Wakamiya, Nobutaka | |||||
| 書誌情報 |
BMC biology 巻 13, 号 27, p. 1-14, 発行日 2015-01-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1741-7007 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1186/s12915-015-0136-2 | |||||
| リンクURL | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | http://bmcbiol.biomedcentral.com/articles/10.1186/s12915-015-0136-2 | http://bmcbiol.biomedcentral.com/articles/10.1186/s12915-015-0136-2 | |||||
| 識別番号 その他 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | PMID:25912189 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | BACKGROUND: \nCollectin-K1 (CL-K1, or CL-11) is a multifunctional Ca(2+)-dependent lectin with roles in innate immunity, apoptosis and embryogenesis. It binds to carbohydrates on pathogens to activate the lectin pathway of complement and together with its associated serine protease MASP-3 serves as a guidance cue for neural crest development. High serum levels are associated with disseminated intravascular coagulation, where spontaneous clotting can lead to multiple organ failure. Autosomal mutations in the CL-K1 or MASP-3 genes cause a developmental disorder called 3MC (Carnevale, Mingarelli, Malpuech and Michels) syndrome, characterised by facial, genital, renal and limb abnormalities. One of these mutations (Gly(204)Ser in the CL-K1 gene) is associated with undetectable levels of protein in the serum of affected individuals. RESULTS: \nIn this study, we show that CL-K1 primarily targets a subset of high-mannose oligosaccharides present on both self- and non-self structures, and provide the structural basis for its ligand specificity. We also demonstrate that three disease-associated mutations prevent secretion of CL-K1 from mammalian cells, accounting for the protein deficiency observed in patients. Interestingly, none of the mutations prevent folding or oligomerization of recombinant fragments containing the mutations in vitro. Instead, they prevent Ca(2+) binding by the carbohydrate-recognition domains of CL-K1. We propose that failure to bind Ca(2+) during biosynthesis leads to structural defects that prevent secretion of CL-K1, thus providing a molecular explanation of the genetic disorder. CONCLUSIONS: \nWe have established the sugar specificity of CL-K1 and demonstrated that it targets high-mannose oligosaccharides on self- and non-self structures via an extended binding site which recognises the terminal two mannose residues of the carbohydrate ligand. We have also shown that mutations associated with a rare developmental disorder called 3MC syndrome prevent the secretion of CL-K1, probably as a result of structural defects caused by disruption of Ca(2+) binding during biosynthesis |
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| 注記 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Creative Commons Attribution License4.0 | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | text | |||||
| 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 | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| ID(XooNIps) | ||||||
| 値 | 25912189 | |||||
| 閲覧数(XooNIps) | ||||||
| 値 | 610 | |||||
| ダウンロード数(XooNIps) | ||||||
| 値 | 897 | |||||
