脂辅因子溶解抑制了原生子的形成
Abigail M Schwind1, Daniel J Walsh1, Cassandra M Burke1
1Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
Journal of neurochemistry
|August 8, 2023
概括
溶解酸乙醇胺 (PE) 的洗剂在实验室中抑制了小鼠的子形成,而不会影响子的子. 这表明膜结构对于子形成至关重要,特别是对于原生PrPC.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生化学
- 分子生物学分子生物学
背景情况:
- 传染性哺乳动物的子需要辅因子分子来进行体外生成.
- 鼠和仓鼠子表现出明显的辅因子偏好,两者都使用PE,仓鼠子使用RNA.
- 洗剂溶解和膜完整性在子形成中的作用仍然不完全理解.
研究的目的:
- 为了研究洗剂溶解对体外动物 prion形成的影响.
- 阐明辅因子溶解对子传播机制的影响.
- 确定膜结构对于辅因子依赖性质素生成的必要性.
主要方法:
- 连续蛋白质错折循环放大 (sPMCA) 反应使用银行脑同质化.
- 测试各种具有不同可溶性酸乙醇胺 (PE) 溶解能力的洗剂.
- 复制的sPMCA反应与纯化的PrPC和辅因子基质 (脂或RNA).
主要成果:
- 溶解PE的洗剂抑制了小鼠离子形成 (RML,Me7,301C菌株) 在它们的临界细胞度 (CMC) 以上.
- 无法溶解PE的洗剂没有影响小鼠的 prion形成.
- 无论PE溶解程度如何,任何测试的洗剂都没有抑制仓鼠 prion 的形成.
- 在复制反应中,n-octylglucoside的抑制与脂发生,但不是RNA辅因子.
- 脂溶解的抑制作用取决于PrPC的翻译后修饰,在重组PrP中没有.
结论:
- 酸乙醇胺 (PE) 促进本源子形成的能力需要脂二层完整性.
- 通过洗剂介导的PE溶解在实验室中抑制了老鼠的质子的形成.
- 膜结构可能在体内质子形成中起着重要作用.
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