BIOMAT Database Logo BIOMAT Database Logo

Effect of cardiac myosin-binding protein C on stability of the thick filament. 2004

G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA.

In contrast to skeletal muscle isoforms of myosin-binding protein C (MyBP-C), the cardiac isoform has 11 rather than 10 modules (labeled C0-C10, N-C terminus), three phosphorylation sites between C1 and C2, and 28 additional amino acids in C5. Within the C5-C10 region of cardiac MyBP-C (cMyBP-C) there are interactions between C5 and C8 as well as C7 and C10. Isolated skinned cardiac trabeculae were incubated with one of three recombinant fragments of cMyBP-C to interfere with interactions of endogenous C5. 2-10 microM C5 or C5-containing peptide fragments of cMyBP-C reversibly reduced Ca sensitivity without extracting myofibrillar protein. C2-C4 fragments had no effect. This result indicated that the region of cMyBP-C that contains C5 maintains a specific structural arrangement of myosin that helps set its contractile properties. Greater than 10 microM C5 caused skinned trabeculae to lose a substantial amount of cMyBP-C and some myosin heavy chain, resulting in irreversible decline in maximum Ca-activated force. MyBP-C appears to stabilize the structure of the thick filament and modulate the way in which myosin heads extend to the thin filament.

UI MeSH Term Description Entries
D008841 Actin Cytoskeleton Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments. Actin Filaments,Microfilaments,Actin Microfilaments,Actin Cytoskeletons,Actin Filament,Actin Microfilament,Cytoskeleton, Actin,Cytoskeletons, Actin,Filament, Actin,Filaments, Actin,Microfilament,Microfilament, Actin,Microfilaments, Actin
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009218 Myosins A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain. Myosin ATPase,ATPase, Actin-Activated,ATPase, Actomyosin,ATPase, Myosin,Actin-Activated ATPase,Actomyosin ATPase,Actomyosin Adenosinetriphosphatase,Adenosine Triphosphatase, Myosin,Adenosinetriphosphatase, Actomyosin,Adenosinetriphosphatase, Myosin,Myosin,Myosin Adenosinetriphosphatase,ATPase, Actin Activated,Actin Activated ATPase,Myosin Adenosine Triphosphatase
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

Related Publications

G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Cardiac myosin binding protein-C is essential for thick-filament stability and flexural rigidity.
April 2009, Biophysical journal,
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Site-specific phosphorylation of myosin binding protein-C coordinates thin and thick filament activation in cardiac muscle.
July 2019, Proceedings of the National Academy of Sciences of the United States of America,
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
The structure of isolated cardiac Myosin thick filaments from cardiac Myosin binding protein-C knockout mice.
March 2008, Biophysical journal,
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Phosphorylation of cardiac myosin binding protein C releases myosin heads from the surface of cardiac thick filaments.
February 2017, Proceedings of the National Academy of Sciences of the United States of America,
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Structure, sarcomeric organization, and thin filament binding of cardiac myosin-binding protein-C.
March 2014, Pflugers Archiv : European journal of physiology,
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Molecular mechanics of cardiac myosin-binding protein C in native thick filaments.
September 2012, Science (New York, N.Y.),
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Myosin binding protein-C phosphorylation is the principal mediator of protein kinase A effects on thick filament structure in myocardium.
November 2012, Journal of molecular and cellular cardiology,
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
N-Terminal Domains of Cardiac Myosin Binding Protein C Cooperatively Activate the Thin Filament.
December 2018, Structure (London, England : 1993),
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Cardiac myosin binding protein C.
May 1999, Circulation research,
G McClellan, and I Kulikovskaya, and J Flavigny, and L Carrier, and S Winegrad
Phosphorylation modulates the mechanical stability of the cardiac myosin-binding protein C motif.
January 2013, Biophysical journal,
Copied contents to your clipboard!