Comparative bioinformatics analysis of prion proteins isolated from reptile, rodent, ruminant, and human species

Abstract

Prion proteins (PrPs) are infectious pathogens that cause a group of invariably fatal, neurodegenerative diseases, including Creutzfeldt-Jakob disease, by means of an entirely novel mechanism. They are produced by various species, including reptile, rodent, ruminant and mammals, during normal metabolic processes, but they can be slowly changed into pathogenic isoforms upon contact with other infectious PrP isoforms. This transmission can occur across species barriers. In the present study, phylogram for each PrP sequence was generated by PAUP* 4.0 program using Neighbor-Joining method with 1,000 times bootstrapping process for the phylogenetic analysis. The molecular dynamics (MD) simulations were performed by the SANDER module in the AMBER 7 package using Amber 99 force field. All the simulation process was conducted in the IBM p690 Supercomputing System in Korea Institute of Science and Technology Information. To reduce the calculation time, we used 'the Generalized Born (GB) model'. We compared the sequences and structural characteristics of normal and pathogenic (E200K) human PrPs with those of other reptile, rodent, ruminant and mammalian PrPs. Phylogenetic analysis revealed that, although the turtle PrP sequence is the most distinct of the PrPs analyzed, it nonetheless retains five conserved secondary structural elements that are similar to those found in the mammalian PrPs, suggesting that these elements have important functions in vivo. The RMS deviation between the normal and E200K human PrPs was larger than that between the normal human and bovine PrPs, and all of the β-sheet structures in human E200K PrP were very stable during MD simulations.

The Cellular Prion Protein Increases the Uptake and Toxicity of TDP-43 Fibrils

“…Despite mouse and human PrP C sequences sharing a high degree of homology [ 46 ], their tertiary structures do not completely overlap, so their expression in a human cell line could result in different biological downstream effects.…”

Molecular dynamics studies on the buffalo prion protein

“…In PDB Bank (www.rcsb.org), bovine PrP has the following PDB entries: 1DWY.pdb, 1DWZ.pdb, 1DX0.pdb, 1DX1.pdb, and 1SKH.pdb. In the PubMed on "bovine prion protein molecular dynamics" we found 1DWY.pdb (Ahn & Son, 2007;Cheng, 2014), 1DWZ.pbb (Herrmann, Gntert, & Wüthrich, 2002), 1DX0.pdb (Kunze et al, 2008) were used. 1DWZ.pdb has 20 structures, and by clustering the 20 structures, we picked up the Number 9 from these 20 structures and we superposed it to 1DWY.pdb and found their RMSD (root mean square deviation) value is 0 Å (however, if we superposed it to 1DX0.pdb, the RMSD is 1.22117 Å).…”