Journal Article

Cryo-EM structure of an amyloid fibril formed by full-length human prion protein

Yin Ping, Li, Dan, Guan Zeyuan, Sun, Yunpeng, Wang, Qiang, Xiang-Ning, Li, Liu, Cong, Chen, Jie, Chuan-Wei, Yi, Li-Qiang, Wang, Han-Ye, Yuan, Tao, Jing, Zhang, Delin, Liang, Yi, Zhao, Kun

2020

نظرة عامة

Prion diseases are caused by the misfolding of prion protein (PrP). Misfolded PrP forms protease-resistant aggregates in vivo (PrPSc) that are able to template the conversion of the native form of the protein (PrPC), a property shared by in vitro–produced PrP fibrils. Here we produced amyloid fibrils in vitro from recombinant, full-length human PrPC (residues 23–231) and determined their structure using cryo-EM, building a model for the fibril core comprising residues 170−229. The PrP fibril consists of two protofibrils intertwined in a left-handed helix. Lys194 and Glu196 from opposing subunits form salt bridges, creating a hydrophilic cavity at the interface of the two protofibrils. By comparison with the structure of PrPC, we propose that two α-helices in the C-terminal domain of PrPC are converted into β-strands stabilized by a disulfide bond in the PrP fibril. Our data suggest that different PrP mutations may play distinct roles in modulating the conformational conversion.A cryo-EM structure of amyloid fibrils formed in vitro with recombinant human PrP provides insights into fibril architecture and the potential role of disease mutations.

• الناشر: Nature Publishing Group
• موضوع: Conversion / Fibrils / Handedness / Helices / Mutation / Prion protein / Protein folding / Proteins / Residues