title: Switching of troponin I: Ca(2+) and myosin-induced activation of heart muscle.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-2041, USA. jmr@uab.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Robinson
authors.forename: Wen-Ji
authors.initials: WJ
authors.lastname: Dong
authors.forename: Jun
authors.initials: J
authors.lastname: Xing
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Cheung
mesh_terms: 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*
chemical_list: D019210:Troponin I; D009218:Myosins; D002118:Calcium