American Chemical Society
bi2012756_si_001.pdf (1.66 MB)

Long-Time Scale Fluctuations of Human Prion Protein Determined by Restrained MD Simulations

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journal contribution
posted on 2011-11-29, 00:00 authored by Massih Khorvash, Guillaume Lamour, Jörg Gsponer
Cellular prion protein (PrPC) has the ability to trigger transmissible lethal diseases after in vivo maturation into a toxic amyloidogenic misfolded form (PrPSc). Here, we use hydrogen exchange protection factors in restrained molecular dynamics simulations to characterize long-time scale fluctuations in human PrPC. We find that the regions of residues 138–141 and 183–192 form new β-strands in several exchange-competent structures. Moreover, these structural changes are associated with the disruption of native contacts that when tethered prevent fibril formation. Our findings illustrate the structural plasticity of PrPC and are valuable for understanding the conversion of PrPC to PrPSc.