ADS-J1 disaggregates semen-derived amyloid fibrils
文献类型：期刊论文
| 作者 | Li, Zhaofeng; Tan, Suiyi; Liu, Shuwen; Zhou, Xuefeng2; Li, Lin; Qiu, Yurong1; Qi, Tao1; Li, Wenjuan; Zhang, Tingting; Qiu, Mengjie |
| 刊名 | BIOCHEMICAL JOURNAL
 |
| 出版日期 | 2019 |
| 卷号 | 476页码:1021 |
| ISSN号 | 0264-6021 |
| DOI | 10.1042/BCJ20180886 |
| 英文摘要 | Semen-derived amyloid fibrils, comprising SEVI (semen-derived enhancer of viral infection) fibrils and SEM1 fibrils, could remarkably enhance HIV-1 sexual transmission and thus are potential targets for the development of an effective microbicide. Previously, we found that ADS-J1, apart from being an HIV-1 entry inhibitor, could also potently inhibit seminal amyloid fibrillization and block fibril-mediated enhancement of viral infection. However, the remodeling effects of ADS-J1 on mature seminal fibrils were unexplored. Herein, we investigated the capacity of ADS-J1 to disassemble seminal fibrils and the potential mode of action by applying several biophysical and biochemical measurements, combined with molecular dynamic (MD) simulations. We found that ADS-J1 effectively remodeled SEVI, SEM1(86-107) fibrils and endogenous seminal fibrils. Unlike epigallocatechin gallate (EGCG), a universal amyloid fibril breaker, ADS-J1 disaggregated SEVI fibrils into monomeric peptides, which was independent of oxidation reaction. MD simulations revealed that ADS-J1 displayed strong binding potency to the full-length PAP(248-286) via electrostatic interactions, hydrophobic interactions and hydrogen bonds. ADS-J1 might initially bind to the fibrillar surface and then occupy the amyloid core, which eventually lead to fibril disassembly. Furthermore, the binding of ADS-J1 with PAP(248-286) might induce conformational changes of PAP(248-286). Disassembled PAP(248-286) might not be favorable to re-aggregate into fibrils. ADS-J1 also exerts abilities to remodel a panel of amyloid fibrils, including A beta(1-42), hIAPP(1-37) and EP2 fibrils. ADS-J1 displays promising potential to be a combination microbicide and an effective lead-product to treat amyloidogenic diseases. |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/17876]  |
| 专题 | 南海海洋研究所_中科院海洋生物资源可持续利用重点实验室 |
| 作者单位 | 1.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Guangdong, Peoples R China 2.Southern Med Univ, Nanfang Hosp, Lab Med Ctr, Guangzhou 510515, Guangdong, Peoples R China 3.Chinese Acad Sci, South China Sea Inst Oceanol, Guangdong Key Lab Marine Mat Med, Key Lab Trop Marine Bioresources & Ecol, Guangzhou 510515, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Zhaofeng,Tan, Suiyi,Liu, Shuwen,et al. ADS-J1 disaggregates semen-derived amyloid fibrils[J]. BIOCHEMICAL JOURNAL,2019,476:1021, 1035. |
| APA | Li, Zhaofeng.,Tan, Suiyi.,Liu, Shuwen.,Zhou, Xuefeng.,Li, Lin.,...&Li, Jinqing.(2019).ADS-J1 disaggregates semen-derived amyloid fibrils.BIOCHEMICAL JOURNAL,476,1021. |
| MLA | Li, Zhaofeng,et al."ADS-J1 disaggregates semen-derived amyloid fibrils".BIOCHEMICAL JOURNAL 476(2019):1021. |
入库方式： OAI收割
来源：南海海洋研究所
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