Aggregation Condition-Structure Relationship of Mouse Prion Protein Fibrils.

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.

• Authors: Jēkabs Fridmanis, Zigmantas Toleikis, Tomas Sneideris, Mantas Ziaunys, Raitis Bobrovs, Vytautas Smirnovas, Kristaps Jaudzems
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 17 (Sep 06 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34502545 (Publication Type: Journal Article)

Chemical References

• Amyloid
• Carbon Isotopes
• Nitrogen Isotopes
• Prion Proteins

Topics

• Amino Acid Sequence
• Amyloid (chemistry, metabolism)
• Animals
• Carbon Isotopes (metabolism)
• Magnetic Resonance Spectroscopy (methods)
• Mice
• Microscopy, Atomic Force (methods)
• Nitrogen Isotopes (metabolism)
• Prion Diseases (metabolism)
• Prion Proteins (chemistry, metabolism)
• Protein Aggregation, Pathological (metabolism)
• Protein Conformation
• Spectroscopy, Fourier Transform Infrared (methods)
• Structure-Activity Relationship