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DOI | 10.1126/science.aao4988 |
Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement | |
Ugurlar, Deniz1; Howes, Stuart C.2; de Kreuk, Bart-Jan3; Koning, Roman I.2,4; de Jong, Rob N.3; Beurskens, Frank J.3; Schuurman, Janine3; Koster, Abraham J.2,4; Sharp, Thomas H.2; Parren, Paul W. H. I.3,5; Gros, Piet1 | |
2018-02-16 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 359期号:6377页码:794-797 |
文章类型 | Article |
语种 | 英语 |
国家 | Netherlands |
英文摘要 | Danger patterns on microbes or damaged host cells bind and activate C1, inducing innate immune responses and clearance through the complement cascade. How these patterns trigger complement initiation remains elusive. Here, we present cryo-electron microscopy analyses of C1 bound to monoclonal antibodies in which we observed heterogeneous structures of single and clustered C1-immunoglobulin G1 (IgG1) hexamer complexes. Distinct C1q binding sites are observed on the two Fc-CH2 domains of each IgG molecule. These are consistent with known interactions and also reveal additional interactions, which are supported by functional IgG1-mutant analysis. Upon antibody binding, the C1q arms condense, inducing rearrangements of the C1r(2)s(2) proteases and tilting C1q's cone-shaped stalk. The data suggest that C1r may activate C1s within single, strained C1 complexes or between neighboring C1 complexes on surfaces. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000425116200045 |
WOS关键词 | C1Q BINDING-SITE ; CRYSTAL-STRUCTURE ; GLOBULAR HEAD ; HUMAN-IGG ; RECRUIT COMPLEMENT ; CATALYTIC DOMAIN ; IMMUNOGLOBULIN-G ; PROTEASE C1R ; C-CHAIN ; B-CHAIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197990 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Utrecht, Bijvoet Ctr Biomol Res, Crystal & Struct Chem, Dept Chem,Fac Sci, Padualaan 8, NL-3584 CH Utrecht, Netherlands; 2.Leiden Univ, Sect Electron Microscopy, Dept Mol Cell Biol, Med Ctr, Einthovenweg 20, NL-2300 RC Leiden, Netherlands; 3.Genmab, Yalelaan 60, NL-3584 CM Utrecht, Netherlands; 4.Leiden Univ, NeCEN, Gorlaeus Labs, NL-2333 CC Leiden, Netherlands; 5.Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands |
推荐引用方式 GB/T 7714 | Ugurlar, Deniz,Howes, Stuart C.,de Kreuk, Bart-Jan,et al. Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement[J]. SCIENCE,2018,359(6377):794-797. |
APA | Ugurlar, Deniz.,Howes, Stuart C..,de Kreuk, Bart-Jan.,Koning, Roman I..,de Jong, Rob N..,...&Gros, Piet.(2018).Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement.SCIENCE,359(6377),794-797. |
MLA | Ugurlar, Deniz,et al."Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement".SCIENCE 359.6377(2018):794-797. |
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