Atomic Structures Suggest Determinants of Transmission Barriers in Mammalian Prion Disease
- 16 February 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 50 (13), 2456-2463
- https://doi.org/10.1021/bi101803k
Abstract
Prion represents a unique class of pathogens devoid of nucleic acid. The deadly diseases transmitted by it between members of one species and, in certain instances, to members of other species present a public health concern. Transmissibility and the barriers to transmission between species have been suggested to arise from the degree to which a pathological protein conformation from an individual of one species can seed a pathological conformation in another species. However, this hypothesis has never been illustrated at an atomic level. Here we present three X-ray atomic structures of the same segment from human, mouse, and hamster PrP, which is critical for forming amyloid and confers species specificity in PrP seeding experiments. The structures reveal that different sequences encode different steric zippers and suggest that the degree of dissimilarity of these zipper structures gives rise to transmission barriers in prion disease, such as those that protect humans from acquiring bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD).Keywords
This publication has 44 references indexed in Scilit:
- Crystallographic Studies of Prion Protein (PrP) Segments Suggest How Structural Changes Encoded by Polymorphism at Residue 129 Modulate Susceptibility to Human Prion DiseasePublished by Elsevier BV ,2010
- Natural and synthetic prion structure from X-ray fiber diffractionProceedings of the National Academy of Sciences of the United States of America, 2009
- Molecular mechanisms for protein-encoded inheritanceNature Structural & Molecular Biology, 2009
- De novo generation of a transmissible spongiform encephalopathy by mouse transgenesisProceedings of the National Academy of Sciences of the United States of America, 2009
- Phasercrystallographic softwareJournal of Applied Crystallography, 2007
- Chronic wasting diseaseBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2007
- Atomic structures of amyloid cross-β spines reveal varied steric zippersNature, 2007
- Structure of the cross-β spine of amyloid-like fibrilsNature, 2005
- Coot: model-building tools for molecular graphicsActa Crystallographica Section D-Structural Biology, 2004
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Structural Biology, 1994