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Molecular dynamics studies on the buffalo prion protein
Jiapu Zhang1,2, Feng Wang1, Subhojyoti Chatterjee1
1a Molecular Model Discovery Laboratory, Faculty of Science, Engineering & Technology, Department of Chemistry & Biotechnology , Swinburne University of Technology , Hawthorn Campus, Hawthorn , Victoria 3122 , Australia.
Journal of Biomolecular Structure & Dynamics
|June 6, 2015
Summary
Buffalo are resistant to prion diseases due to unique molecular structures in their cellular prion protein (PrP(C)). These structural differences, including specific hydrogen bonds and salt bridges, prevent the misfolding associated with transmissible spongiform encephalopathies (TSEs).
Area of Science:
- Molecular biology
- Neuroscience
- Structural biology
Background:
- Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases caused by misfolded prion proteins.
- Buffalo exhibit low susceptibility to TSEs, unlike many other species.
- The normal cellular prion protein (PrP(C)) converts to an abnormal, infectious form (PrP(Sc)) rich in beta-sheets.
Purpose of the Study:
- To investigate the molecular structure and dynamics of buffalo PrP(C) (BufPrP(C)).
- To elucidate the structural basis for buffalo's resistance to prion diseases.
Main Methods:
- Homology modeling of BufPrP(C) based on bovine PrP NMR structure.
- Molecular dynamics simulations to analyze structural dynamics and interactions.
- Identification of hydrogen bonds, salt bridges, and other molecular interactions.
Main Results:
- BufPrP(C) possesses unique structural features, including five hydrogen bonds at Asn143, absent in cattle.
- A stable salt bridge (Asp178-Arg164) and a strong hydrogen bond (Ser170-Tyr218) stabilize the β2-α2 loop.
- Additional stabilizing interactions, including a salt bridge (His187-Arg156) and π-π stacking, were identified.
Conclusions:
- Specific structural characteristics of BufPrP(C) contribute to its resistance against prion disease.
- The identified hydrogen bonds and salt bridges likely prevent the conformational changes leading to PrP(Sc) formation.
- Understanding these structural differences provides insights into prion disease mechanisms and interspecies resistance.
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