Molecular dynamics studies on the NMR structures of rabbit prion protein wild-type and mutants: surface electrostatic charge distributions

TL;DR

This study uses molecular dynamics simulations to analyze rabbit prion protein structures, revealing how surface electrostatic charge distributions influence their stability and potentially contribute to rabbits' low susceptibility to prion diseases.

Contribution

It provides new insights into the role of surface electrostatic charges in prion protein stability, based on MD simulations of rabbit prion structures and mutants.

Findings

Electrostatic charge distributions affect prion protein stability.

Wild-type rabbit prion proteins show stable electrostatic surface properties.

Mutations alter surface charge distributions and potentially stability.

Abstract

Prion is a misfolded protein found in mammals that causes infectious diseases of the nervous system in humans and animals. Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elk and humans etc. Recent studies have shown that rabbits have a low susceptibility to be infected by prion diseases with respect to other animals including humans. The present study employs molecular dynamics (MD) means to unravel the mechanism of rabbit prion proteins (RaPrPC) based on the recently available rabbit NMR structures (of the wild-type and its two mutants of two surface residues). The electrostatic charge distributions on the protein surface are the focus when analysing the MD trajectories. It is found that we can conclude that surface electrostatic charge distributions indeed contribute to the structural stability of wild-type RaPrPC; this may be useful for the medicinal treatment of prion diseases.