The C-terminally truncated Y145Stop variant of prion protein (PrP23-144) has been linked to a heritable prionopathy in humans and is also capable of triggering a transmissible prion disease in mice. PrP23-144 can be converted from soluble monomeric form to amyloid under physiological conditions, providing an in vitro model for investigating the molecular basis of amyloid strains and cross-seeding barriers. Here, we use magic-angle spinning solid-state NMR to establish the sequential backbone and sidechain ¹³C and ¹⁵N chemical shift assignments for amyloid fibrils formed by the A117V and M129V mutants of human PrP23-144, which in the context of full length PrP in vivo are among the specific residues associated with development of Gerstmann–Straüssler–Scheinker disease. The chemical shift data are utilized to identify amino acids comprising the rigid amyloid core regions and to predict the protein secondary structures for human PrP23-144 A117V and M129V fibrils.

朊病毒蛋白的 C 末端截短的 Y145Stop 变体 (PrP23-144) 与人类可遗传的朊病毒病有关，并且还能够在小鼠中引发传染性朊病毒病。PrP23-144 可以在生理条件下从可溶性单体形式转化为淀粉样蛋白，为研究淀粉样蛋白菌株的分子基础和交叉播种屏障提供了体外模型。在这里，我们使用魔角旋转固态 NMR 来建立顺序主链和侧链¹³ C 和¹⁵由人 PrP23-144 的 A117V 和 M129V 突变体形成的淀粉样蛋白原纤维的 N 化学位移分配，在体内全长 PrP 的背景下，是与 Gerstmann-Straüssler-Scheinker 病发展相关的特定残基之一。化学位移数据用于鉴定包含刚性淀粉样蛋白核心区域的氨基酸并预测人 PrP23-144 A117V 和 M129V 原纤维的蛋白质二级结构。