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PDBsum entry 5a36
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Structural protein
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PDB id
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5a36
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References listed in PDB file
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Key reference
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Title
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Hypertrophic cardiomyopathy mutations in the calponin-Homology domain of actn2 affect actin binding and cardiomyocyte z-Disc incorporation.
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Authors
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N.J.Haywood,
M.Wolny,
B.Rogers,
C.H.Trinh,
Y.Shuping,
T.A.Edwards,
M.Peckham.
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Ref.
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Biochem J, 2016,
473,
2485-2493.
[DOI no: ]
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PubMed id
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Abstract
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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.
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