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Updated: Jul 20, 2025

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
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Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling

Published on: August 1, 2016

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Divalent ions as mediators of carbonylation in cardiac myosin binding protein C

Christina Bergonzo1, Baikuntha Aryal2, V Ashutosh Rao2

  • 1Institute for Bioscience and Biotechnology Research, National Institute of Standards and Technology, the University of Maryland, 9600 Gudelsky Way, Rockville, MD, 20850, USA.

Journal of Molecular Graphics & Modelling
|August 3, 2023
PubMed

Insights

Chemotherapy drug toxicity may stem from metal-induced damage to cardiac myosin binding protein C (cMyBP-C). This study reveals metal ions near cMyBP-C may disrupt its actin binding, impacting heart function.

Area of Science:

  • Biochemistry
  • Cardiovascular Science
  • Computational Biology

Background:

  • Chemotherapeutic drug efficacy is often limited by off-pathway toxicities.
  • Cardiac myosin binding protein C (cMyBP-C) in heart tissue is a potential target for metal-catalyzed oxidative damage.
  • Previous studies link metal ions and reactive oxygen species to protein carbonylation, altering protein structure and function.

Purpose of the Study:

  • To investigate the ion environment around the C0 and C1 subunits of cMyBP-C.
  • To explore the relationship between metal ions, protein carbonylation, and actin-cMyBP-C binding.
  • To understand the molecular mechanisms underlying chemotherapy-induced cardiotoxicity.

Main Methods:

  • Long timescale all-atom molecular dynamics simulations were employed.
  • The study focused on the C0 and C1 subunits of cMyBP-C, crucial for actin binding.
  • Analysis of ion localization and its correlation with carbonylation-prone amino acid residues.

Main Results:

  • Divalent cations were found to be co-localized with amino acid residues susceptible to carbonylation within cMyBP-C.
  • Carbonylation of these specific residues can lead to interruptions in the binding between actin and cMyBP-C.
  • This suggests a potential mechanism for metal-induced cardiotoxicity.

Conclusions:

  • Metal ion accumulation near critical binding sites on cMyBP-C is implicated in chemotherapy-related cardiotoxicity.
  • Site-specific carbonylation of cMyBP-C by metal ions can disrupt its function in cardiac muscle.
  • These findings highlight the need for strategies to mitigate metal-induced damage during chemotherapy.
Keywords:
Metal ion-induced ROSMolecular dynamicsProtein carbonylationcMyBP-C

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