类似于apidaecin的的序列多样性阻止了终结的核糖体
Weiping Huang1, Chetana Baliga1, Nora Vázquez-Laslop1
1Department of Pharmaceutical Sciences and Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Nucleic acids research
|July 2, 2024
概括
富含的抗微生物 (PrAMPs),如阿皮德,可以阻止细菌的转化. 这项研究确定了许多具有改变序列的apidaecin变体,这些变体保留了核糖体逮捕活性,有些表现出增强的抗菌作用.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 众所周知,富含的抗微生物 (PrAMPs) 可以抑制细菌的转化.
- 阿皮素 (Api) 是一种18氨基酸PrAMP,通过与核糖体新生的退出道结合而起作用.
- 虫捕捉释放因子 (RF1/RF2) 并在停止密码子时逮捕核糖体,停止蛋白质合成.
研究的目的:
- 为了研究apidaecin的序列变异性,维持其核糖体翻译抑制活性.
- 识别具有潜在治疗应用的 PrAMP 新型变体.
主要方法:
- 在细菌细胞中表达的合成突变虫素基因的大型图书馆 (约35万个变体) 的选.
- 应用直角负和正选择策略来识别功能变异.
- 评价选择的多替代阿皮代辛变体的抗菌活性.
主要成果:
- 识别了多个具有多个替代物的多个apidaecin变体,这些变体保留了在停止码子时捕获核糖体的能力.
- 证明了特定氨基酸残留在apidaecin功能中的关键作用.
- 发现了几种合成的多替代阿皮德辛变体,与野生类型阿皮德辛相比,它们表现出增强的抗菌活性.
结论:
- 特定的氨基酸残留对于apidaecin的核糖体停止功能至关重要.
- 广泛的PrAMP序列可以准终结核糖体.
- 工程化apidaecin变体显示出希望作为开发新的临床抗微生物药物的起点.
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