2N0A

Atomic-resolution structure of alpha-synuclein fibrils


Experimental Data Snapshot

  • Method: SOLID-STATE NMR
  • Conformers Calculated: 256 
  • Conformers Submitted: 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Solid-state NMR structure of a pathogenic fibril of full-length human alpha-synuclein.

Tuttle, M.D.Comellas, G.Nieuwkoop, A.J.Covell, D.J.Berthold, D.A.Kloepper, K.D.Courtney, J.M.Kim, J.K.Barclay, A.M.Kendall, A.Wan, W.Stubbs, G.Schwieters, C.D.Lee, V.M.George, J.M.Rienstra, C.M.

(2016) Nat Struct Mol Biol 23: 409-415

  • DOI: https://doi.org/10.1038/nsmb.3194
  • Primary Citation of Related Structures:  
    2N0A

  • PubMed Abstract: 

    Misfolded α-synuclein amyloid fibrils are the principal components of Lewy bodies and neurites, hallmarks of Parkinson's disease (PD). We present a high-resolution structure of an α-synuclein fibril, in a form that induces robust pathology in primary neuronal culture, determined by solid-state NMR spectroscopy and validated by EM and X-ray fiber diffraction. Over 200 unique long-range distance restraints define a consensus structure with common amyloid features including parallel, in-register β-sheets and hydrophobic-core residues, and with substantial complexity arising from diverse structural features including an intermolecular salt bridge, a glutamine ladder, close backbone interactions involving small residues, and several steric zippers stabilizing a new orthogonal Greek-key topology. These characteristics contribute to the robust propagation of this fibril form, as supported by the structural similarity of early-onset-PD mutants. The structure provides a framework for understanding the interactions of α-synuclein with other proteins and small molecules, to aid in PD diagnosis and treatment.


  • Organizational Affiliation

    Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-synuclein
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J
140Homo sapiensMutation(s): 0 
Gene Names: SNCANACPPARK1
UniProt & NIH Common Fund Data Resources
Find proteins for P37840 (Homo sapiens)
Explore P37840 
Go to UniProtKB:  P37840
PHAROS:  P37840
GTEx:  ENSG00000145335 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP37840
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLID-STATE NMR
  • Conformers Calculated: 256 
  • Conformers Submitted: 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-23
    Type: Initial release
  • Version 1.1: 2016-05-11
    Changes: Database references
  • Version 1.2: 2016-05-18
    Changes: Database references
  • Version 1.3: 2016-06-01
    Changes: Structure summary
  • Version 1.4: 2023-06-14
    Changes: Data collection, Database references, Other
  • Version 1.5: 2024-05-15
    Changes: Data collection, Database references