Imperial College London

ProfessorMarinvan Heel

Faculty of Natural SciencesDepartment of Life Sciences

Visiting Professor



+44 (0)20 7594 5316m.vanheel Website




Dr Audrey Geffen +44 (0)20 7594 5323




G20Flowers buildingSouth Kensington Campus






BibTex format

author = {Vázquez-Fernández, E and Vos, MR and Afanasyev, P and Cebey, L and Sevillano, AM and Vidal, E and Rosa, I and Renault, L and Ramos, A and Peters, PJ and Fernández, JJ and van, Heel M and Young, HS and Requena, JR and Wille, H},
doi = {10.1371/journal.ppat.1005835},
journal = {PLOS Pathogens},
title = {The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy},
url = {},
volume = {12},
year = {2016}

RIS format (EndNote, RefMan)

AB - The structure of the infectious prion protein (PrPSc), which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protein (PrPC) into the misfolded, infectious conformer through an unknown mechanism. PrPSc and its N-terminally truncated variant, PrP 27-30, aggregate into amorphous aggregates, 2D crystals, and amyloid fibrils. The structure of these infectious conformers is essential to understanding prion replication and the development of structure-based therapeutic interventions. Here we used the repetitive organization inherent to GPI-anchorless PrP 27-30 amyloid fibrils to analyze their structure via electron cryomicroscopy. Fourier-transform analyses of averaged fibril segments indicate a repeating unit of 19.1 Å. 3D reconstructions of these fibrils revealed two distinct protofilaments, and, together with a molecular volume of 18,990 Å3, predicted the height of each PrP 27-30 molecule as ~17.7 Å. Together, the data indicate a four-rung β-solenoid structure as a key feature for the architecture of infectious mammalian prions. Furthermore, they allow to formulate a molecular mechanism for the replication of prions. Knowledge of the prion structure will provide important insights into the self-propagation mechanisms of protein misfolding.
AU - Vázquez-Fernández,E
AU - Vos,MR
AU - Afanasyev,P
AU - Cebey,L
AU - Sevillano,AM
AU - Vidal,E
AU - Rosa,I
AU - Renault,L
AU - Ramos,A
AU - Peters,PJ
AU - Fernández,JJ
AU - van,Heel M
AU - Young,HS
AU - Requena,JR
AU - Wille,H
DO - 10.1371/journal.ppat.1005835
PY - 2016///
SN - 1553-7366
TI - The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy
T2 - PLOS Pathogens
UR -
UR -
VL - 12
ER -