2KES

Solution Structure of the Coiled-coil Domain of Synphilin-1


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication.

Xie, Y.Y.Zhou, C.J.Zhou, Z.R.Hong, J.Che, M.X.Fu, Q.S.Song, A.X.Lin, D.H.Hu, H.Y.

(2010) FASEB J 24: 196-205

  • DOI: https://doi.org/10.1096/fj.09-133082
  • Primary Citation of Related Structures:  
    2JN5, 2KES

  • PubMed Abstract: 

    alpha-Synuclein (alpha-Syn) is the major component of Lewy bodies (LBs) deposited in the brains of patients with Parkinson's disease. Synphilin-1 (Sph1) is a novel alpha-Syn-interacting protein also present in the LBs. However, the roles of alpha-Syn-Sph1 interaction in LB formation and in the related pathogenesis are still unclear. We have studied the interaction between alpha-Syn and Sph1 by biochemical and structural approaches and found that the central coiled-coil domain of Sph1 specifically interacts with the N-terminal stretch of alpha-Syn. When overexpressed in HEK 293T cells, Sph1 forms inclusions together with alpha-Syn, but the Sph1-positive inclusions cannot recruit the N-terminally truncated alpha-Syn. The central portion of Sph1 can also recruit alpha-Syn and induce inclusion formation through its coiled-coil domain. These observations demonstrate that the alpha-Syn-Sph1 interaction significantly promotes the formation of cytoplasmic alpha-Syn inclusions, which may have implications for LB formation in neural cells. We have also elucidated solution structure of the coiled-coil domain of Sph1 and its interaction with the N-terminal peptide of alpha-Syn. The specific interaction between alpha-Syn and Sph1 provides mechanistic insights into the inclusion-body formation in cells and pathological implication in Parkinson's disease.


  • Organizational Affiliation

    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Synphilin-148Homo sapiensMutation(s): 0 
Gene Names: SNCAIP
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y6H5 (Homo sapiens)
Explore Q9Y6H5 
Go to UniProtKB:  Q9Y6H5
PHAROS:  Q9Y6H5
GTEx:  ENSG00000064692 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y6H5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2022-03-16
    Changes: Data collection, Database references, Derived calculations
  • Version 1.3: 2024-05-29
    Changes: Data collection