5A36

Mutations in the Calponin homology domain of Alpha-Actinin-2 affect Actin binding and incorporation in muscle.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Hypertrophic Cardiomyopathy Mutations in the Calponin-Homology Domain of Actn2 Affect Actin Binding and Cardiomyocyte Z-Disc Incorporation.

Haywood, N.Wolny, M.Rogers, B.Trinh, C.H.Shuping, Y.Edwards, T.A.Peckham, M.

(2016) Biochem J 473: 2485

  • DOI: https://doi.org/10.1042/BCJ20160421
  • Primary Citation of Related Structures:  
    5A36, 5A37, 5A38, 5A4B

  • PubMed Abstract: 

    α-Actinin-2 (ACTN2) is the only muscle isoform of α-actinin expressed in cardiac muscle. Mutations in this protein have been implicated in mild to moderate forms of hypertrophic cardiomyopathy (HCM). We have investigated the effects of two mutations identified from HCM patients, A119T and G111V, on the secondary and tertiary structure of a purified actin binding domain (ABD) of ACTN2 by circular dichroism and X-ray crystallography, and show small but distinct changes for both mutations. We also find that both mutants have reduced F-actin binding affinity, although the differences are not significant. The full length mEos2 tagged protein expressed in adult cardiomyocytes shows that both mutations additionally affect Z-disc localization and dynamic behaviour. Overall, these two mutations have small effects on structure, function and behaviour, which may contribute to a mild phenotype for this disease.


  • Organizational Affiliation

    Astbury Centre for Structural Molecular Biology and the School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ALPHA-ACTININ-2
A, B
250Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P35609 (Homo sapiens)
Explore P35609 
Go to UniProtKB:  P35609
PHAROS:  P35609
GTEx:  ENSG00000077522 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35609
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.220 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.658α = 80.78
b = 47.491β = 80.8
c = 70.299γ = 76.5
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
Aimlessdata scaling
REFMACphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-22
    Type: Initial release
  • Version 1.1: 2016-08-24
    Changes: Database references
  • Version 1.2: 2024-05-08
    Changes: Data collection, Database references, Other