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Aggregation of PrP106-126 on surfaces of neutral and negatively charged membranes studied by molecular dynamics simulations



Aggregation of PrP106-126 on surfaces of neutral and negatively charged membranes studied by molecular dynamics simulations



Biochimica et Biophysica Acta. Biomembranes 2018:



Prion diseases are neurodegenerative disorders characterized by the aggregation of an abnormal form of prion protein. The interaction of prion protein and cellular membrane is crucial to elucidate the occurrence and development of prion diseases. Its fragment, residues 106-126, has been proven to maintain the pathological properties of misfolded prion and was used as a model peptide. In this study, explicit solvent molecular dynamics (MD) simulations were carried out to investigate the adsorption, folding and aggregation of PrP106-126 with different sizes (2-peptides, 4-peptides and 6-peptides) on the surface of both pure neutral POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and negatively charged POPC/POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol) (3:1) lipids. MD simulation results show that PrP106-126 display strong affinity with POPC/POPG but does not interact with pure POPC. The positively charged and polar residues participating hydrogen bonding with membrane promote the adsorption of PrP106-126. The presence of POPC and POPC/POPG exert limited influence on the secondary structures of PrP106-126 and random coil structures are predominant in all simulation systems. Upon the adsorption on the POPC/POPG surface, the aggregation states of PrP106-126 have been changed and more small oligomers were observed. This work provides insights into the interactions of PrP106-126 and membranes with different compositions in atomic level, which expand our understanding the role membrane plays in the development of prion diseases. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy.

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Accession: 045573631

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PMID: 29550288

DOI: 10.1016/j.bbamem.2018.03.009


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