Sub-ångström cryo-EM structure of a prion protofibril reveals a polar clasp

The atomic structure of the infectious, protease-resistant, β -sheet-rich and fibrillar mammalian prion remains unknown. Through the cryo-EM method MicroED, we reveal the sub-ångström-resolution structure of a protofibril formed by a wild-type segment from the β 2– α 2 loop of the bank vole prion pr...

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Published in:	Nature structural & molecular biology Vol. 25; no. 2; pp. 131 - 134
Main Authors:	Gallagher-Jones, Marcus, Glynn, Calina, Boyer, David R., Martynowycz, Michael W., Hernandez, Evelyn, Miao, Jennifer, Zee, Chih-Te, Novikova, Irina V., Goldschmidt, Lukasz, McFarlane, Heather T., Helguera, Gustavo F., Evans, James E., Sawaya, Michael R., Cascio, Duilio, Eisenberg, David S., Gonen, Tamir, Rodriguez, Jose A.
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-02-2018 Nature Publishing Group
Subjects:	101/28 631/45/535/1258/1259 631/535/1266/1265 692/699 Amyloid - chemistry Amyloidogenic Proteins - chemistry Animals Atomic structure Banks (Finance) Biochemistry Biological Microscopy Biological research Biomedical and Life Sciences Bonds (Securities) Brief Communication Carbamazepine - chemistry Cattle Cricetinae Cryoelectron Microscopy Deer Electrons Fasteners Genomics Humans Hydrogen Hydrogen Bonding Hydrogen bonds Laboratories Life Sciences Membrane Biology Mice Molecular biology Nanocrystals Peptides Peptides - chemistry Phylogeny Physiological aspects Prion protein Prions (Proteins) Prions - chemistry Proteases Protein Structure Protein Structure, Secondary Proteins Proteome Proteomics Sheep Structure Surface Properties X-Ray Diffraction X-rays United States
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Summary:	The atomic structure of the infectious, protease-resistant, β -sheet-rich and fibrillar mammalian prion remains unknown. Through the cryo-EM method MicroED, we reveal the sub-ångström-resolution structure of a protofibril formed by a wild-type segment from the β 2– α 2 loop of the bank vole prion protein. The structure of this protofibril reveals a stabilizing network of hydrogen bonds that link polar zippers within a sheet, producing motifs we have named ‘polar clasps’. MicroED structure of a peptide from the β2–α2 loop of the bank vole prion protein reveals a protofibril stabilized by a dense network of hydrogen bonds.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 NSFOTHERHHMI Author contributions: J.A.R. directed the work. J.A.R., J.M., E.H., M.W.M. and C.G. grew, evaluated and optimized crystals. J.A.R., D.R.B., C.G., M.R.S., H.T.M., M.G.J., C.Z., I.V.N, J.E.E. and D.C. collected data. J.A.R., C.G., J.M., M.G.J., M.R.S., D.C., M.W.M., G.H., E.H., L.G., D.S.E., and T.G. analyzed the data. C.G., M.G.J. and J.A.R. wrote the article, with input from all authors.
ISSN:	1545-9993 1545-9985
DOI:	10.1038/s41594-017-0018-0