An essential myosin light chain peptide induces supramaximal stimulation of cardiac myofibrillar ATPase activity.
The N-terminal region of skeletal myosin light chain-1 (MLC-1) binds to the C terminus of actin, yet the functional significance of this interaction is unclear. We studied a fragment (MLC-pep; residues 5-14) of the ventricular MLC-1. When added to rat cardiac myofibrils, 10 nM MLC-pep induced a supramaximal increase in the MgATPase activity at submaximal Ca2+ levels with no effect at low and maximal Ca2+ levels. A nonsense, scrambled sequence peptide had no effect at any pCa value. MLC-pep did not affect myosin KEDTA and CaATPase activities or actin-activated MgATPase activities in the absence or presence of tropomyosin. The MLC-pep did not alter the ability of troponin I to inhibit MgATPase activity. Moreover, when troponin I and troponin C were extracted from the myofibrils, the MLC-pep lost its ability to stimulate the ATPase rate. This effect was fully restored upon reconstitution of the extracted myofibrils with troponin I-troponin C complex. Thus, activation of MgATPase activity by the peptide required a full complement of thin filament regulatory proteins. Interestingly, the stimulatory effect occurred at a ratio of 4 peptides to 1 thin filament, suggesting that the peptide engages in a highly cooperative process that may involve activation of the entire thin filament.
Department of Physiology and Biophysics, College of Medicine, University of Illinois, Chicago, Illinois 60612-7342, USA.
H M
HM
Rarick
T J
TJ
Opgenorth
T W
TW
von Geldern
J R
JR
Wu-Wong
R J
RJ
Solaro
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D006352:Heart Ventricles / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D018994:Myosin Light Chains / Q000737:chemistry*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function
D009124:Muscle Proteins; D018994:Myosin Light Chains; D010446:Peptide Fragments; D000251:Adenosine Triphosphatases