SARS-CoV-2 蛋白质片段对结构稳定性,氨基原性潜力和α-Synuclein 聚合的明显影响
Vince St Dollente Mesias1, Jianing Zhang1, Hongni Zhu1,2
1Department of Chemistry, The, Hong Kong University of Science and Technology, Clearwater Bay Road, Kowloon, Hong Kong SAR, China.
Chembiochem : a European journal of chemical biology
|October 31, 2024
概括
SARS-CoV-2 蛋白质部分可以形成粉样纤维,可能与神经退行有关. 修改病毒序列 (SK9) 改变了它的稳定性和聚合性,影响了神经元蛋白 (αSyn) 的形成.
科学领域:
- 生物化学 生化学
- 神经科学是一个神经科学.
- 病毒学 病毒学
背景情况:
- 氨基粉症涉及错误折叠的蛋白质积累,导致疾病.
- SARS-CoV-2的蛋白质段涉及粉体发生和潜在的神经退行.
- 将病毒蛋白与神经退行症联系在一起的机制尚不清楚.
研究的目的:
- 调查SARS-CoV-2包膜蛋白段 (SK9) 的结构,稳定性和氨基原性潜力.
- 评估SK9对神经元蛋白α-synuclein (αSyn) 聚合的影响.
- 探索序列修改以调节病毒氨基基代.
主要方法:
- 合成和特征野生型SK9和两个变体 (SK9 var1,SK9 var2) 带有变化的电荷和疏水性.
- 评估了SK9的amyloidogenic倾向,结构和稳定性.
- 研究了SK9野生型对αSyn聚合动力学和聚合性质的影响.
主要成果:
- 野生型SK9由于不稳定性而表现出高的粉原性倾向;变体是稳定的,非粉原性.
- SK9野生型显著影响了αSyn聚合动力学和形态学.
- 在SK9野生型存在时形成的αSyn聚合物表现出对酶降解的抗性增加.
结论:
- 短序列的修改可以控制粉样蛋白的形成特性.
- 病毒蛋白段可能通过αSyn聚合促进神经退行.
- 研究结果提供了对病毒诱导的粉样蛋白聚合和潜在的治疗策略的见解.
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