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Aggregation Condition-Structure Relationship of Mouse Prion Protein Fibrils.

Published version
Peer-reviewed

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Type

Article

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Authors

Toleikis, Zigmantas 
Ziaunys, Mantas 
Bobrovs, Raitis 

Abstract

Prion diseases are associated with conformational conversion of cellular prion protein into a misfolded pathogenic form, which resembles many properties of amyloid fibrils. The same prion protein sequence can misfold into different conformations, which are responsible for variations in prion disease phenotypes (prion strains). In this work, we use atomic force microscopy, FTIR spectroscopy and magic-angle spinning NMR to devise structural models of mouse prion protein fibrils prepared in three different denaturing conditions. We find that the fibril core region as well as the structure of its N- and C-terminal parts is almost identical between the three fibrils. In contrast, the central part differs in length of β-strands and the arrangement of charged residues. We propose that the denaturant ionic strength plays a major role in determining the structure of fibrils obtained in a particular condition by stabilizing fibril core interior-facing glutamic acid residues.

Description

Keywords

aggregation conditions, amyloid, fibril structure, prion protein, Amino Acid Sequence, Amyloid, Animals, Carbon Isotopes, Magnetic Resonance Spectroscopy, Mice, Microscopy, Atomic Force, Nitrogen Isotopes, Prion Diseases, Prion Proteins, Protein Aggregation, Pathological, Protein Conformation, Spectroscopy, Fourier Transform Infrared, Structure-Activity Relationship

Journal Title

Int J Mol Sci

Conference Name

Journal ISSN

1661-6596
1422-0067

Volume Title

22

Publisher

MDPI AG