Faculty of Electronics, Telecommunications and Informatics, Gdansk University of Technology, G. Narutowicza 11/12, 80-233 Gdansk, Poland.
Department of Chemistry & Biochemistry, University of Oklahoma, Norman, Oklahoma 73019,United States.
J Phys Chem B. 2022 Aug 25;126(33):6221-6230. doi: 10.1021/acs.jpcb.2c04614. Epub 2022 Aug 16.
Prion diseases are characterized by the conversion of prion proteins from a PrP fold into a disease-causing PrP form that is self-replicating. A possible agent to trigger this conversion is polyadenosine RNA, but both mechanism and pathways of the conversion are poorly understood. Using coarse-grained molecular dynamic simulations we study the time evolution of PrP over 600 μs. We find that both the D178N mutation and interacting with polyadenosine RNA reduce the helicity of the protein and encourage formation of segments with strand-like motifs. We conjecture that these transient β-strands nucleate the conversion of the protein to the scrapie conformation PrP.
朊病毒疾病的特征是朊病毒蛋白从 PrP 折叠构象转变成具有自我复制能力的致病构象。多聚腺苷酸 RNA 可能是引发这种转变的一种物质，但这种转变的机制和途径尚不清楚。我们使用粗粒化分子动力学模拟研究了 PrP 在 600 μs 内的时间演化。我们发现，D178N 突变和与多聚腺苷酸 RNA 相互作用都会降低蛋白质的螺旋性，并促使形成具有链状模体的片段。我们推测这些短暂的β-折叠是蛋白质向瘙痒病构象 PrP 转变的核心。
