Crystal Structure of a Human Prion Protein Fragment Reveals a Motif for Oligomer Formation

The structural transition of the prion protein from α-helical- to β-sheet-rich underlies its conversion into infectious and disease-associated isoforms. Here we describe the crystal structure of a fragment from human prion protein consisting of the disulfide-bond-linked portions of helices 2 and 3....

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Bibliographic Details
Published in:Journal of the American Chemical Society 2013-07, Vol.135 (28), p.10202-10205
Main Authors: Apostol, Marcin I, Perry, Kay, Surewicz, Witold K
Format: Article
Language:English
Subjects:
Crystallography, X-Ray
Humans
Models, Molecular
Prions - chemistry
Protein Conformation
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Summary:The structural transition of the prion protein from α-helical- to β-sheet-rich underlies its conversion into infectious and disease-associated isoforms. Here we describe the crystal structure of a fragment from human prion protein consisting of the disulfide-bond-linked portions of helices 2 and 3. Instead of forming a pair-of-sheets steric zipper structure characteristic of amyloid fibers, this fragment crystallized into a β-sheet-rich assembly of hexameric oligomers. This study reveals a never before observed structural motif for ordered protein aggregates and suggests a possible mechanism for self-propagation of misfolded conformations by such nonamyloid oligomers.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja403001q