Structural and functional insights into a novel two-component endolysin encoded by a single gene in Enterococcus faecalis phage
文献类型：期刊论文
| 作者 | Zhou, B; Zhen, XK; Zhou, H; Zhao, FY; Fan, CP; Perculija, V; Tong, YG; Mi, ZQ; Ouyang, SY |
| 刊名 | PLOS PATHOGENS
 |
| 出版日期 | 2020 |
| 卷号 | 16期号:3页码:- |
| ISSN号 | 1553-7366 |
| 关键词 | CRYSTAL-STRUCTURE BACTERIOPHAGE ENDOLYSINS STAPHYLOCOCCUS-AUREUS DIABETIC FOOT LYSIN RECOGNITION MECHANISM PROTEIN |
| DOI | 10.1371/journal.ppat.1008394 |
| 文献子类 | 期刊论文 |
| 英文摘要 | Using bacteriophage-derived endolysins as an alternative strategy for fighting drug-resistant bacteria has recently been garnering renewed interest. However, their application is still hindered by their narrow spectra of activity. In our previous work, we demonstrated that the endolysin LysIME-EF1 possesses efficient bactericidal activity against multiple strains of Enterococcus faecalis (E. faecalis). Herein, we observed an 8 kDa fragment and hypothesized that it contributes to LysIME-EF1 lytic activity. To examine our hypothesis, we determined the structure of LysIME-EF1 at 1.75 angstrom resolution. LysIME-EF1 exhibits a unique architecture in which one full-length LysIME-EF1 forms a tetramer with three additional C-terminal cell-wall binding domains (CBDs) that correspond to the abovementioned 8 kDa fragment. Furthermore, we identified an internal ribosomal binding site (RBS) and alternative start codon within LysIME-EF1 gene, which are demonstrated to be responsible for the translation of the truncated CBD. To elucidate the molecular mechanism for the lytic activity of LysIME-EF1, we combined mutagenesis, lytic activity assays and in vivo animal infection experiments. The results confirmed that the additional LysIME-EF1 CBDs are important for LysIME-EF1 architecture and its lytic activity. To our knowledge, this is the first determined structure of multimeric endolysin encoded by a single gene in E. faecalis phages. As such, it may provide valuable insights into designing potent endolysins against the opportunistic pathogen E. faecalis. Author summary LysIME-EF1, an endolysin that lyses E. faecalis, displays the prospect of treating E. faecalis infection. We find that the C-terminal cell-wall binding domain (CBD) is important for the lytic activity of LysIME-EF1. By determining the crystal structures of wild type (WT) LysIME-EF1 and its C-terminal CBD, this study reveals how the holoenzyme is organized to carry out its highly efficient lytic activity. Our finding provides structural and functional evidence that LysIME-EF1 belongs to a unique two-component multimeric endolysin encoded by a single gene. |
| 语种 | 英语 |
| 源URL | [http://ir.sinap.ac.cn/handle/331007/33154]  |
| 专题 | 上海应用物理研究所_中科院上海应用物理研究所2011-2017年 |
| 作者单位 | 1.Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing Adv Innovat Ctr Soft Matter Sci & Engn BA, Beijing, Peoples R China 2.Fujian Normal Univ, Prov Univ Key Lab Cellular Stress Response & Meta, Key Lab Innate Immune Biol Fujian Prov,Minist Edu, Biomed Res Ctr South China,Key Lab OptoElect Sci, Fuzhou, Peoples R China 3.Pilot Natl Lab Marine Sci & Technol Qingdao, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai, Peoples R China 5.Wuhan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Wuhan, Peoples R China 6.Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, B,Zhen, XK,Zhou, H,et al. Structural and functional insights into a novel two-component endolysin encoded by a single gene in Enterococcus faecalis phage[J]. PLOS PATHOGENS,2020,16(3):-. |
| APA | Zhou, B.,Zhen, XK.,Zhou, H.,Zhao, FY.,Fan, CP.,...&Ouyang, SY.(2020).Structural and functional insights into a novel two-component endolysin encoded by a single gene in Enterococcus faecalis phage.PLOS PATHOGENS,16(3),-. |
| MLA | Zhou, B,et al."Structural and functional insights into a novel two-component endolysin encoded by a single gene in Enterococcus faecalis phage".PLOS PATHOGENS 16.3(2020):-. |
入库方式： OAI收割
来源：上海应用物理研究所
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