Switching of troponin I: Ca(2+) and myosin-induced activation of heart muscle.
The principal task of the Ca(2+) activation of striated muscle is the release of the troponin I (TnI) inhibitory region (TnI-I) from actin. TnI-I release facilitates the repositioning of tropomyosin across the actin surface and the formation of strong, force generating, actin-myosin cross-bridges. Full activation of the Ca(2+) regulatory switch (CRS) requires two switching steps in cTnI: binding of the TnI regulatory region to hydrophobic sites in the N-domain of Ca(2+)-bound troponin C and release of the adjacent TnI-I from actin. Using Förster resonance energy transfer, we have examined the requirements for full activation of the cardiac CRS. In the presence of actin, both Ca(2+) and strong cross-bridges are required for full activation. Actin desensitizes the CRS to Ca(2+) and produces cooperativity in the Ca(2+) activation of the CRS. Strong cross-bridges eliminate cooperativity and re-sensitize the CRS to Ca(2+). We propose a kinetic scheme and a structural model to account for these findings.
Robinson
John M
JM
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-2041, USA. jmr@uab.edu
Dong
Wen-Ji
WJ
Xing
Jun
J
Cheung
Herbert C
HC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005453:Fluorescence; D051379:Mice; D016296:Mutagenesis; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D051381:Rats; D019210:Troponin I / Q000235:genetics / Q000378:metabolism*
D019210:Troponin I; D009218:Myosins; D002118:Calcium