2M55

NMR structure of the complex of an N-terminally acetylated alpha-synuclein peptide with calmodulin


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

NMR Structure of Calmodulin Complexed to an N-Terminally Acetylated alpha-Synuclein Peptide.

Gruschus, J.M.Yap, T.L.Pistolesi, S.Maltsev, A.S.Lee, J.C.

(2013) Biochemistry 52: 3436-3445

  • DOI: https://doi.org/10.1021/bi400199p
  • Primary Citation of Related Structures:  
    2M55

  • PubMed Abstract: 

    Calmodulin (CaM) is a calcium binding protein that plays numerous roles in Ca-dependent cellular processes, including uptake and release of neurotransmitters in neurons. α-Synuclein (α-syn), one of the most abundant proteins in central nervous system neurons, helps maintain presynaptic vesicles containing neurotransmitters and moderates their Ca-dependent release into the synapse. Ca-Bound CaM interacts with α-syn most strongly at its N-terminus. The N-terminal region of α-syn is important for membrane binding; thus, CaM could modulate membrane association of α-syn in a Ca-dependent manner. In contrast, Ca-free CaM has negligible interaction. The interaction with CaM leads to significant signal broadening in both CaM and α-syn NMR spectra, most likely due to conformational exchange. The broadening is much reduced when binding a peptide consisting of the first 19 residues of α-syn. In neurons, most α-syn is acetylated at the N-terminus, and acetylation leads to a 10-fold increase in binding strength for the α-syn peptide (KD = 35 ± 10 μM). The N-terminally acetylated peptide adopts a helical structure at the N-terminus with the acetyl group contacting the N-terminal domain of CaM and with less ordered helical structure toward the C-terminus of the peptide contacting the CaM C-terminal domain. Comparison with known structures shows that the CaM/α-syn complex most closely resembles Ca-bound CaM in a complex with an IQ motif peptide. However, a search comparing the α-syn peptide sequence with known CaM targets, including IQ motifs, found no homologies; thus, the N-terminal α-syn CaM binding site appears to be a novel CaM target sequence.


  • Organizational Affiliation

    Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calmodulin148Homo sapiensMutation(s): 0 
Gene Names: 
CALM1CALMCAMCAM1CALM2CAM2CAMBCALM3CALML2CAM3...
CALM1CALMCAMCAM1CALM2CAM2CAMBCALM3CALML2CAM3CAMCCAMIII

UniProt & NIH Common Fund Data Resources
Find proteins for P0DP23 (Homo sapiens)
Explore P0DP23 
Go to UniProtKB:  P0DP23
PHAROS:  P0DP23
GTEx:  ENSG00000198668 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DP23
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-synuclein21Homo sapiensMutation(s): 2 
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: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-05-08
    Type: Initial release
  • Version 1.1: 2013-12-18
    Changes: Database references
  • Version 1.2: 2013-12-25
    Changes: Source and taxonomy
  • Version 1.3: 2023-06-14
    Changes: Data collection, Database references, Derived calculations, Other