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 various internal organs. It is known that lysozyme fibrils show polymorphism and that polymorphs formed at near-neutral pH have the ability to promote more monomer binding than those...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.812096/full |
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| author | Tatsuhito Matsuo Tatsuhito Matsuo Tatsuhito Matsuo Alessio De Francesco Alessio De Francesco Judith Peters Judith Peters Judith Peters |
| author_facet | Tatsuhito Matsuo Tatsuhito Matsuo Tatsuhito Matsuo Alessio De Francesco Alessio De Francesco Judith Peters Judith Peters Judith Peters |
| author_sort | Tatsuhito Matsuo |
| collection | DOAJ |
| description | Lysozyme amyloidosis is a hereditary disease, which is characterized by the deposition of lysozyme amyloid fibrils in various internal organs. It is known that lysozyme fibrils show polymorphism and that polymorphs formed at near-neutral pH have the ability to promote more monomer binding than those formed at acidic pH, indicating that only specific polymorphs become dominant species in a given environment. This is likely due to the polymorph-specific configurational diffusion. Understanding the possible differences in dynamical behavior between the polymorphs is thus crucial to deepen our knowledge of amyloid polymorphism 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 human lysozyme, 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 motions is similar for both LP27 and LP60, LP60 contains a larger fraction of atoms moving with larger amplitudes than LP27, indicating that the dynamical difference between the two polymorphs lies not in the averaged amplitude, but in the distribution of the amplitudes. 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 dynamics of the two lysozyme polymorphs and reveals that the molecular dynamics of LP60 is enhanced compared with that of LP27. The higher molecular flexibility of the polymorph would permit to adjust its conformation more quickly than its counterpart, facilitating monomer binding. |
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| last_indexed | 2024-12-24T01:45:10Z |
| publishDate | 2022-01-01 |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-4d3b87a9850b455ba57320dcb71ba8352022-12-21T17:21:53ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-01-01810.3389/fmolb.2021.812096812096Molecular Dynamics of Lysozyme Amyloid Polymorphs Studied by Incoherent Neutron ScatteringTatsuhito Matsuo0Tatsuhito Matsuo1Tatsuhito Matsuo2Alessio De Francesco3Alessio De Francesco4Judith Peters5Judith Peters6Judith Peters7Univ. Grenoble Alpes, CNRS, LiPhy, Grenoble, FranceInstitut Laue-Langevin, Grenoble, FranceInstitute for Quantum Life Science, National Institutes for Quantum Science and Technology, Tokai, JapanInstitut Laue-Langevin, Grenoble, FranceCNR-IOM and INSIDE@ILL C/O Operative Group in Grenoble (OGG), Grenoble, FranceUniv. Grenoble Alpes, CNRS, LiPhy, Grenoble, FranceInstitut Laue-Langevin, Grenoble, FranceInstitut Universitaire de France, Paris, FranceLysozyme amyloidosis is a hereditary disease, which is characterized by the deposition of lysozyme amyloid fibrils in various internal organs. It is known that lysozyme fibrils show polymorphism and that polymorphs formed at near-neutral pH have the ability to promote more monomer binding than those formed at acidic pH, indicating that only specific polymorphs become dominant species in a given environment. This is likely due to the polymorph-specific configurational diffusion. Understanding the possible differences in dynamical behavior between the polymorphs is thus crucial to deepen our knowledge of amyloid polymorphism 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 human lysozyme, 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 motions is similar for both LP27 and LP60, LP60 contains a larger fraction of atoms moving with larger amplitudes than LP27, indicating that the dynamical difference between the two polymorphs lies not in the averaged amplitude, but in the distribution of the amplitudes. 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 dynamics of the two lysozyme polymorphs and reveals that the molecular dynamics of LP60 is enhanced compared with that of LP27. The higher molecular flexibility of the polymorph would permit to adjust its conformation more quickly than its counterpart, facilitating monomer binding.https://www.frontiersin.org/articles/10.3389/fmolb.2021.812096/fullelastic incoherent neutron scatteringquasi-elastic neutron scatteringlysozyme amyloidosispolymorphismamyloid fibrilsprotein dynamics |
| spellingShingle | Tatsuhito Matsuo Tatsuhito Matsuo Tatsuhito Matsuo Alessio De Francesco Alessio De Francesco Judith Peters Judith Peters Judith Peters Molecular Dynamics of Lysozyme Amyloid Polymorphs Studied by Incoherent Neutron Scattering Frontiers in Molecular Biosciences elastic incoherent neutron scattering quasi-elastic neutron scattering lysozyme amyloidosis polymorphism amyloid fibrils protein dynamics |
| title | Molecular Dynamics of Lysozyme Amyloid Polymorphs Studied by Incoherent Neutron Scattering |
| title_full | Molecular Dynamics of Lysozyme Amyloid Polymorphs Studied by Incoherent Neutron Scattering |
| title_fullStr | Molecular Dynamics of Lysozyme Amyloid Polymorphs Studied by Incoherent Neutron Scattering |
| title_full_unstemmed | Molecular Dynamics of Lysozyme Amyloid Polymorphs Studied by Incoherent Neutron Scattering |
| title_short | Molecular Dynamics of Lysozyme Amyloid Polymorphs Studied by Incoherent Neutron Scattering |
| title_sort | molecular dynamics of lysozyme amyloid polymorphs studied by incoherent neutron scattering |
| topic | elastic incoherent neutron scattering quasi-elastic neutron scattering lysozyme amyloidosis polymorphism amyloid fibrils protein dynamics |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.812096/full |
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