Altered interactions between cardiac myosin binding protein-c and α-cardiac actin variants associated with cardiomyopathies

Melissa L. Chow, Justin F. Shaffer, Samantha P. Harris, John F. Dawson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The two genes most commonly associated with mutations linked to hypertrophic or dilated cardiomyopathies are β-myosin and cardiac myosin binding protein-C (cMyBP-C). Both of these proteins interact with cardiac actin (ACTC). Currently there are 16 ACTC variants that have been found in patients with HCM or DCM. While some of these ACTC variants exhibit protein instability or polymerization-deficiencies that might contribute to the development of disease, other changes could cause changes in protein-protein interactions between sarcomere proteins and ACTC. To test the hypothesis that changes in ACTC disrupt interactions with cMyBP-C, we examined the interactions between seven ACTC variants and the N-terminal C0C2 fragment of cMyBP-C. We found there was a significant decrease in binding affinity (increase in Kd values) for the A331P and Y166C variants of ACTC. These results suggest that a change in the ability of cMyBP-C to bind actin filaments containing these ACTC protein variants might contribute to the development of disease. These results also provide clues regarding the binding site of the C0C2 fragment of cMyBP-C on F-actin.

Original languageEnglish (US)
Pages (from-to)28-32
Number of pages5
JournalArchives of Biochemistry and Biophysics
Volume550-551
DOIs
StatePublished - May 15 2014
Externally publishedYes

Fingerprint

Cardiac Myosins
Cardiomyopathies
Actins
Carrier Proteins
Proteins
Sarcomeres
Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Myosins
Actin Cytoskeleton
Polymerization
Genes
Binding Sites
Mutation
myosin-binding protein C

Keywords

  • Cardiac actin
  • Cardiomyopathy
  • Heart disease
  • Myosin binding protein-C

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Altered interactions between cardiac myosin binding protein-c and α-cardiac actin variants associated with cardiomyopathies. / Chow, Melissa L.; Shaffer, Justin F.; Harris, Samantha P.; Dawson, John F.

In: Archives of Biochemistry and Biophysics, Vol. 550-551, 15.05.2014, p. 28-32.

Research output: Contribution to journalArticle

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