Molecular dynamics studies on the NMR and X-ray structures of rabbit prion protein wild-type and mutants

TL;DR

This study uses molecular dynamics to analyze NMR and X-ray structures of rabbit prion proteins, aiming to understand their unique resistance to prion diseases and the effects of mutations.

Contribution

It provides detailed MD analysis of rabbit prion structures, revealing insights into their conformational stability and resistance mechanisms compared to other species.

Findings

Rabbit prion proteins show distinct conformational stability.

Mutations affect prion structure and potential infectivity.

MD simulations suggest mechanisms for low susceptibility.

Abstract

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep, goats, mice, humans, chimpanzees, hamsters, cattle, elks, deer, minks, cats, chicken, pigs, turtles, etc. These neurodegenerative diseases are caused by the conversion from a soluble normal cellular protein into insoluble abnormally folded infectious prions and the conversion is believed to involve conformational change from a predominantly alpha-helical protein to one rich in beta-sheet structure. Such conformational changes may be amenable to study by molecular dynamics (MD) techniques. For rabbits, classical studies show they have a low susceptibility to be infected, but in 2012 it was reported that rabbit prion can be generated (though not directly) and the rabbit prion is infectious and transmissible (Proceedings of the National Academy of Sciences USA 109(13): 5080-5). This paper studies the NMR and X-ray molecular structures of rabbit prion protein wild-type and mutants by MD techniques, in order to understand the specific mechanism of rabbit prion protein and rabbit prions.