Your browser doesn't support javascript.
loading
Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue.
Dhavale, Dhruva D; Barclay, Alexander M; Borcik, Collin G; Basore, Katherine; Gordon, Isabelle R; Liu, Jialu; Milchberg, Moses H; O'shea, Jennifer; Rau, Michael J; Smith, Zachary; Sen, Soumyo; Summers, Brock; Smith, John; Warmuth, Owen A; Chen, Qian; Fitzpatrick, James A J; Schwieters, Charles D; Tajkhorshid, Emad; Rienstra, Chad M; Kotzbauer, Paul T.
Afiliação
  • 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; Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110, 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 J; Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Rau MJ; Washington University 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 61
  • Summers B; Washington University 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, IL 61801, USA.
  • Warmuth OA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Chen Q; Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, IL 61801, USA.
  • Fitzpatrick JAJ; Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Schwieters CD; Computational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Tajkhorshid E; 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 61
  • Rienstra CM; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • Kotzbauer PT; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
bioRxiv ; 2023 Jan 10.
Article em En | MEDLINE | ID: mdl-36711931
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. We developed and validated a novel method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and used solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise two protofilaments with pseudo-21 helical screw symmetry, very low twist and an interface formed by antiparallel beta strands of residues 85-93. The 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 landscape of LBD Asyn fibrils and inform further studies of disease mechanisms, imaging agents and therapeutics targeting Asyn.
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article