Asset Details
Do you wish to reserve the book?
Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin
Do you wish to request the book?
Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin
2019
Overview
Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) accelerates cardiac contractility. However, the mechanisms by which cMyBP-C phosphorylation increases contractile kinetics have not been fully elucidated. In this study, we tested the hypothesis that phosphorylation of cMyBP-C releases myosin heads from the inhibited super-relaxed state (SRX), thereby determining the fraction of myosin available for contraction. Mice with various alanine (A) or aspartic acid (D) substitutions of the three main phosphorylatable serines of cMyBP-C (serines 273, 282, and 302) were used to address the association between cMyBP-C phosphorylation and SRX. Single-nucleotide turnover in skinned ventricular preparations demonstrated that phosphomimetic cMyBP-C destabilized SRX, whereas phosphoablated cMyBP-C had a stabilizing effect on SRX. Strikingly, phosphorylation at serine 282 site was found to play a critical role in regulating the SRX. Treatment of WT preparations with protein kinase A (PKA) reduced the SRX, whereas, in nonphosphorylatable cMyBP-C preparations, PKA had no detectable effect. Mice with stable SRX exhibited reduced force production. Phosphomimetic cMyBP-C with reduced SRX exhibited increased rates of tension redevelopment and reduced binding to myosin. We also used recombinant myosin subfragment-2 to disrupt the endogenous interaction between cMyBP-C and myosin and observed a significant reduction in the population of SRX myosin. This peptide also increased force generation and rate of tension redevelopment in skinned fibers. Taken together, this study demonstrates that the phosphorylation-dependent interaction between cMyBP-C and myosin is a determinant of the fraction of myosin available for contraction. Furthermore, the binding between cMyBP-C and myosin may be targeted to improve contractile function.
Publisher
National Academy of Sciences
Subject
/ Alanine
/ Animals
/ Cardiac Myosins - metabolism
/ Carrier Proteins - metabolism
/ Cyclic AMP-Dependent Protein Kinases - metabolism
/ Cytoskeletal Proteins - metabolism
/ Heart
/ Kinases
/ Kinetics
/ Mice
/ Myocardial Contraction - physiology
/ Myocytes, Cardiac - metabolism
/ Myosin
/ Myosin Subfragments - metabolism
/ Phosphorylation - physiology
/ Proteins
/ Serine
/ Skin
We currently cannot retrieve any items related to this title. Kindly check back at a later time.