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How graphene affects the misfolding of human prion protein: A combined experimental and molecular dynamics simulation study
- Zhu, Yongchang, Guo, Jingjing, Zhang, Ai, Li, Lanlan, Liu, Xuewei, Liu, Huanxiang, Yao, Xiaojun
- Environmental research 2019 v.171 pp. 1-10
- adsorption, amyloid, circular dichroism spectroscopy, fluorescence, graphene, humans, molecular dynamics, prion diseases, prions, risk, solvents, van der Waals forces
- As the broad application of graphene in the biomedical field, it is urgent and important to evaluate how the graphene affects the structure and function of the proteins in our body, especially the amyloid-related proteins. Prion protein, as a typical amyloid protein, it misfolding and aggregation will lead to serious prion diseases. To explore if graphene promotes or inhibits the formation of amyloid, here, we combined the experimental and molecular dynamics (MD) simulation methods to study the influence of graphene on the globular domain of prion protein (PrP117–231). The results from fluorescence quenching and circular dichroism spectrum showed that the addition of graphene changed the secondary structure of prion protein largely, mainly reflecting in the reduced α-helix structure and the increased coil structure, indicating graphene may strengthen the misfolding inclination of prion. To further uncover the mechanism of conformational change of prion under the induction of graphene, the all-atoms MD simulations in explicit solvent were performed. Our simulations suggest that prion protein can be quickly and tightly adsorbed onto graphene together with the weak conformational rearrangement and may reorient when approaching the surface. The Van der Waals' force drive the adsorption process. In the induction of graphene, H1 and S2-H2 loop regions of prion become unstable and prion begins to misfold partially. Our work shows that graphene can induce the misfolding of prion protein and may cause the potential risk to biosystems.