6LNI

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

Summary for 6LNI

• Entry DOI: 10.2210/pdb6lni/pdb
• EMDB information: 0931
• Descriptor: Major prion protein (1 entity in total)
• Functional Keywords: amyloid fibril, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 10
• Total formula weight: 229963.55

Authors

Wang, L.Q.,Zhao, K.,Yuan, H.Y.,Wang, Q.,Guan, Z.Y.,Tao, J.,Li, X.N.,Hao, M.M.,Chen, J.,Zhang, D.L.,Zhu, H.L.,Yin, P.,Liu, C.,Liang, Y. (deposition date: 2019-12-30, release date: 2020-06-10, Last modification date: 2024-10-09)

Primary citation

Wang, L.Q.,Zhao, K.,Yuan, H.Y.,Wang, Q.,Guan, Z.,Tao, J.,Li, X.N.,Sun, Y.,Yi, C.W.,Chen, J.,Li, D.,Zhang, D.,Yin, P.,Liu, C.,Liang, Y.
Cryo-EM structure of an amyloid fibril formed by full-length human prion protein.
Nat.Struct.Mol.Biol., 27:598-602, 2020

PubMed Abstract: Prion diseases are caused by the misfolding of prion protein (PrP). Misfolded PrP forms protease-resistant aggregates in vivo (PrP) that are able to template the conversion of the native form of the protein (PrP), a property shared by in vitro-produced PrP fibrils. Here we produced amyloid fibrils in vitro from recombinant, full-length human PrP (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 PrP, we propose that two α-helices in the C-terminal domain of PrP 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.

PubMed: 32514176
DOI: 10.1038/s41594-020-0441-5

Experimental method

ELECTRON MICROSCOPY (2.702 Å)