Journal Article

FZJ-2014-06732

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Progress towards structural understanding of infectious sheep PrP-amyloid

Müller, H. ; Brener, O. ; Andreoletti, O. ; Piechatzek, T.FZJ* ; Willbold, D.FZJ* ; Legname, G. ; Heise, H. (Corresponding Author)FZJ*

2014
Landes Bioscience Austin, Tex.

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Please use a persistent id in citations: doi:10.4161/19336896.2014.983754

Abstract: The still elusive structural difference of non-infectious and infectious amyloid of the mammalian prion protein (PrP) is a major pending milestone in understanding protein-mediated infectivity in neurodegenerative diseases. Preparations of PrP-amyloid proven to be infectious have never been investigated with a high-resolution technique. All available models to date have been based on low-resolution data. Here, we establish protocols for the preparation of infectious samples of full-length recombinant (rec) PrP¡amyloid in NMR-sufficient amounts by spontaneous fibrillation and seeded fibril growth from brain extract. We link biological and structural data of infectious recPrP-amyloid, derived from bioassays, atomic force microscopy, and solid-state NMR spectroscopy. Our data indicate a semi-mobile N‑terminus, some residues with secondary chemical shifts typical of α‑helical secondary structure in the middle part between ~115 to ~155, and a distinct β‑sheet core C‑terminal of residue ~155. These findings are not in agreement with all current models for PrP-amyloid. We also provide evidence that samples seeded from brain extract may not differ in the overall arrangement of secondary structure elements, but rather in the flexibility of protein segments outside the β-core region. Taken together, our protocols provide an essential basis for the high-resolution characterization of non-infectious and infectious PrP-amyloid in the near future.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 452 - Structural Biology (POF2-452) (POF2-452)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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