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

Marcus Gallagher-Jones; Calina Glynn; David R Boyer; Michael W Martynowycz; Evelyn Hernandez; Jennifer Miao; Chih-Te Zee; Irina V Novikova; Lukasz Goldschmidt; Heather T McFarlane; Gustavo F Helguera; James E Evans; Michael R Sawaya; Duilio Cascio; David S Eisenberg; Tamir Gonen; Jose A Rodriguez

doi:10.1038/s41594-017-0018-0

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

Nat Struct Mol Biol. 2018 Feb;25(2):131-134. doi: 10.1038/s41594-017-0018-0. Epub 2018 Jan 15.

Authors

Marcus Gallagher-Jones¹, Calina Glynn¹, David R Boyer², Michael W Martynowycz³, Evelyn Hernandez¹, Jennifer Miao¹, Chih-Te Zee¹, Irina V Novikova⁴, Lukasz Goldschmidt², Heather T McFarlane², Gustavo F Helguera⁵, James E Evans⁴, Michael R Sawaya², Duilio Cascio², David S Eisenberg², Tamir Gonen³, Jose A Rodriguez⁶

Affiliations

¹ Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA, USA.
² Department of Biological Chemistry and Department of Chemistry and Biochemistry, University of California Los Angeles, Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, CA, USA.
³ Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
⁴ Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA.
⁵ Laboratory of Pharmaceutical Biotechnology, Institute of Biology and Experimental Medicine, Buenos Aires, Argentina.
⁶ Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA, USA. jrodriguez@mbi.ucla.edu.

Abstract

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 β2-α2 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'.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amyloid / chemistry*
Amyloidogenic Proteins / chemistry
Animals
Carbamazepine / chemistry
Cattle
Cricetinae
Cryoelectron Microscopy*
Deer
Electrons
Humans
Hydrogen Bonding*
Mice
Peptides / chemistry
Phylogeny
Prions / chemistry*
Protein Structure, Secondary
Proteome
Sheep
Surface Properties
X-Ray Diffraction

Substances

Amyloid
Amyloidogenic Proteins
Peptides
Prions
Proteome
Carbamazepine

Abstract

Publication types

MeSH terms

Substances

Grants and funding