Molecular dynamics of lysozyme amyloid polymorphs studied by incoherent neutron scattering

Lysozyme amyloidosis is a hereditary disease, which is characterized by the deposition of lysozyme amyloid fibrils in variousinternal organs. It is known that lysozyme fibrils show polymorphism and that polymorphs formed at near-neutral pH have theability to promote more monomer binding than those formed at acidic pH, indicating that only specific polymorphs becomedominant species in a given environment. This is likely due to the polymorph-specific configurational diffusion. Understanding thepossible differences in dynamical behavior between the polymorphs is thus crucial to deepen our knowledge of amyloidpolymorphism and eventually elucidate the molecular mechanism of lysozyme amyloidosis. In this study, molecular dynamics at sub-nanosecond timescale of two kinds of polymorphic fibrils of hen egg white lysozyme, which has long been used as a model of humanlysozyme, formed at pH 2.7 (LP27) and pH 6.0 (LP60) was investigated using elastic incoherent neutron scattering (EINS) and quasi-elastic neutron scattering (QENS). Analysis of the EINS data showed that whereas the mean square displacement of atomic motionsis similar for both LP27 and LP60, LP60 contains a larger fraction of atoms moving with larger amplitudes than LP27, indicatingthat the dynamical difference between the two polymorphs lies not in the averaged amplitude, but in the distribution of theamplitudes. Furthermore, analysis of the QENS data showed that the jump diffusion coefficient of atoms is larger for LP60,suggesting that the atoms of LP60 undergo faster diffusive motions than those of LP27. This study thus characterizes the dynamicsof the two lysozyme polymorphs and reveals that the molecular dynamics of LP60 is enhanced compared with that of LP27. Thehigher molecular flexibility of the polymorph would permit to adjust its conformation more quickly than its counterpart,facilitating monomer binding.