SARS-CoV-2 刺突蛋白片段可减轻α-突触核蛋白的淀粉样变性。
SARS-COV-2 spike protein fragment eases amyloidogenesis of α-synuclein.
机构信息
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, USA.
出版信息
J Chem Phys. 2023 Jul 7;159(1). doi: 10.1063/5.0157331.
Abstract
Parkinson's disease is accompanied by the presence of amyloids in the brain that are formed of α-synuclein chains. The correlation between COVID-19 and the onset of Parkinson's disease led to the idea that amyloidogenic segments in SARS-COV-2 proteins can induce aggregation of α-synuclein. Using molecular dynamic simulations, we show that the fragment FKNIDGYFKI of the spike protein, which is unique for SARS-COV-2, preferentially shifts the ensemble of α-synuclein monomer toward rod-like fibril seeding conformations and, at the same time, differentially stabilizes this polymorph over the competing twister-like structure. Our results are compared with earlier work relying on a different protein fragment that is not specific for SARS-COV-2.
摘要
帕金森病伴随着大脑中由α-突触核蛋白链组成的淀粉样蛋白的存在。COVID-19 与帕金森病发病之间的相关性使得人们想到，SARS-CoV-2 蛋白中的淀粉样蛋白片段可以诱导α-突触核蛋白的聚集。使用分子动力学模拟，我们表明，棘突蛋白的片段 FKNIDGYFKI 是 SARS-CoV-2 所特有的，优先将α-突触核蛋白单体的集合体向棒状原纤维成核构象转移，同时使这种多晶型体相对于竞争的扭曲构象更稳定。我们的结果与早期依赖于非 SARS-CoV-2 特异性的不同蛋白片段的工作进行了比较。
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