Imperial College London
Alternate

ProfessorMarinvan Heel

Faculty of Natural Sciences, Department of Life Sciences

Visiting Professor
 
 
 
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Contact

 

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

 
 
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Assistant

 

Dr Audrey Geffen +44 (0)20 7594 5323

 
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Location

 

G20Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Vázquez-Fernández:2016:10.1371/journal.ppat.1005835,
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 = {http://dx.doi.org/10.1371/journal.ppat.1005835},
volume = {12},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
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  - http://dx.doi.org/10.1371/journal.ppat.1005835
UR  - http://hdl.handle.net/10044/1/41714
VL  - 12
ER  -
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