Related Experiment Video

Updated: Jun 23, 2025

A Sensitive and Specific Quantitation Method for Determination of Serum Cardiac Myosin Binding Protein-C by Electrochemiluminescence Immunoassay
10:12

A Sensitive and Specific Quantitation Method for Determination of Serum Cardiac Myosin Binding Protein-C by Electrochemiluminescence Immunoassay

Published on: August 8, 2013

16.7K

Cardiac myosin binding protein-C phosphorylation as a function of multiple protein kinase and phosphatase activities

Thomas Kampourakis1, Saraswathi Ponnam1, Kenneth S Campbell2

  • 1Randall Centre for Cell and Molecular Biophysics; and British Heart Foundation Centre of Research Excellence, King's College London, London, SE1 1UL, United Kingdom.

Nature Communications
|June 14, 2024
PubMed

Insights

Protein phosphatases 1 and 2A (PP1 and PP2A) regulate cardiac myosin binding protein-C (cMyBP-C) dephosphorylation with site-specificity. This study reveals their distinct roles in cardiac function and heart failure.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Enzymology

Background:

  • Cardiac myosin binding protein-C (cMyBP-C) phosphorylation regulates cardiac myofilament function.
  • The role of protein phosphatases in cMyBP-C dephosphorylation is largely unknown.
  • Protein kinases' influence on cMyBP-C phosphorylation is well-documented.

Purpose of the Study:

  • To biochemically characterize cMyBP-C dephosphorylation by protein phosphatases 1 and 2A (PP1 and PP2A).
  • To develop an integrated kinetic model for cMyBP-C phosphorylation.
  • To investigate the roles of PP1 and PP2A in physiological and heart failure conditions.

Main Methods:

  • Detailed biochemical characterization of cMyBP-C dephosphorylation by PP1 and PP2A.
  • Development of an integrated kinetic model incorporating data for phosphatases and kinases.
  • Experimental validation of model predictions using human patient data.

Main Results:

  • PP1 and PP2A exhibit strong site-specificity and hierarchical dephosphorylation mechanisms for cMyBP-C.
  • The dephosphorylation pathway is opposite to the sequential phosphorylation pathway by protein kinase A.
  • The integrated kinetic model accurately predicts complex, non-linear cMyBP-C phosphorylation patterns.

Conclusions:

  • PP1 and PP2A play non-redundant roles in regulating cMyBP-C.
  • These phosphatases are crucial for cMyBP-C regulation in both normal and failing hearts.
  • Understanding phosphatase activity is vital for cardiac function and disease.

More Related Videos

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling08:29

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

Published on: August 1, 2016

9.5K
Probing Myosin Ensemble Mechanics in Actin Filament Bundles Using Optical Tweezers06:53

Probing Myosin Ensemble Mechanics in Actin Filament Bundles Using Optical Tweezers

Published on: May 4, 2022

2.2K

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.3K
Overview of Myosin Structure and Function01:15

Overview of Myosin Structure and Function

Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X)  have been well...
4.2K
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.3K
Actin and Myosin in Muscle Contraction01:16

Actin and Myosin in Muscle Contraction

Actin and myosin are contractile proteins that form the sarcomere found in skeletal muscle tissues for regulating muscle contraction. Actin, a globular contractile protein, interacts with myosin for muscle contraction. The skeletal tissue appears striped or striated under a microscope due to the repeated arrangement of contractile proteins actin and myosin along the length of myofibrils. Dark A bands and light I bands repeat along myofibrils, and the alignment of myofibrils in the cell causes...
10.0K