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DOI | 10.1126/science.aar1999 |
Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B | |
Chen, Peng1; Tao, Liang2,3; Wang, Tianyu1; Zhang, Jie2,3; He, Aina2,3,4; Lam, Kwok-ho1; Liu, Zheng1; He, Xi5; Perry, Kay6,7; Dong, Min2,3; Jin, Rongsheng1 | |
2018-05-11 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 360期号:6389页码:664-669 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China |
英文摘要 | Clostridium difficile infection is the most common cause of antibiotic-associated diarrhea in developed countries. The major virulence factor, C. difficile toxin B (TcdB), targets colonic epithelia by binding to the frizzled (FZD) family of Wnt receptors, but how TcdB recognizes FZDs is unclear. Here, we present the crystal structure of a TcdB fragment in complex with the cysteine-rich domain of human FZD2 at 2.5-angstrom resolution, which reveals an endogenous FZD-bound fatty acid acting as a co-receptor for TcdB binding. This lipid occupies the binding site for Wnt-adducted palmitoleic acid in FZDs. TcdB binding locks the lipid in place, preventing Wnt from engaging FZDs and signaling. Our findings establish a central role of fatty acids in FZD-mediated TcdB pathogenesis and suggest strategies to modulate Wnt signaling. |
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:000431790900048 |
WOS关键词 | GLUCOSYLATING TOXINS ; INFECTION ; DISEASE ; RECEPTORS ; PATHOGENESIS ; DIMERIZATION ; VIRULENCE ; BINDING ; MODEL |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
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/198623 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA; 2.Harvard Med Sch, Boston Childrens Hosp, Dept Urol, Dept Microbiol & Immunobiol, Boston, MA 02115 USA; 3.Harvard Med Sch, Dept Surg, Boston, MA 02115 USA; 4.Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Oncol, 600 Yishan Rd, Shanghai 200233, Peoples R China; 5.Harvard Med Sch, Dept Neurol, Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA USA; 6.Cornell Univ, Argonne Natl Lab, NE CAT, Argonne, IL USA; 7.Cornell Univ, Argonne Natl Lab, Dept Chem & Chem Biol, Argonne, IL USA |
推荐引用方式 GB/T 7714 | Chen, Peng,Tao, Liang,Wang, Tianyu,et al. Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B[J]. SCIENCE,2018,360(6389):664-669. |
APA | Chen, Peng.,Tao, Liang.,Wang, Tianyu.,Zhang, Jie.,He, Aina.,...&Jin, Rongsheng.(2018).Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B.SCIENCE,360(6389),664-669. |
MLA | Chen, Peng,et al."Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B".SCIENCE 360.6389(2018):664-669. |
条目包含的文件 | 条目无相关文件。 |
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