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Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue.
Dhavale, Dhruva D; Barclay, Alexander M; Borcik, Collin G; Basore, Katherine; Berthold, Deborah A; Gordon, Isabelle R; Liu, Jialu; Milchberg, Moses H; O'Shea, Jennifer Y; Rau, Michael J; Smith, Zachary; Sen, Soumyo; Summers, Brock; Smith, John; Warmuth, Owen A; Perrin, Richard J; Perlmutter, Joel S; Chen, Qian; Fitzpatrick, James A J; Schwieters, Charles D; Tajkhorshid, Emad; Rienstra, Chad M; Kotzbauer, Paul T.
Affiliation
  • Dhavale DD; Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Barclay AM; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
  • Borcik CG; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
  • Basore K; Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Berthold DA; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
  • Gordon IR; Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Liu J; Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Milchberg MH; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
  • O'Shea JY; Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Rau MJ; Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Smith Z; Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Sen S; Theoretical and Computational Biophysics Group, NIH Resource for Macromolecular Modeling and Visualization, Beckman Institute for Advanced Science and Technology, Department of Biochemistry, and Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 6
  • Summers B; Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Smith J; Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
  • Warmuth OA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
  • Perrin RJ; Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Perlmutter JS; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Chen Q; Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Fitzpatrick JAJ; Department of Radiology, Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Schwieters CD; Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
  • Tajkhorshid E; Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Rienstra CM; Computational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Kotzbauer PT; Theoretical and Computational Biophysics Group, NIH Resource for Macromolecular Modeling and Visualization, Beckman Institute for Advanced Science and Technology, Department of Biochemistry, and Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 6
Nat Commun ; 15(1): 2750, 2024 Mar 29.
Article in En | MEDLINE | ID: mdl-38553463
ABSTRACT
The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Parkinson Disease / Lewy Body Disease Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Parkinson Disease / Lewy Body Disease Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: Estados Unidos