Characterization of the Ca2+-switch in skeletal and cardiac muscles.
To determine the significance of the global structure of the regulatory proteins in the mechanism of the Ca2+-switch in cardiac and skeletal muscle contractions, the properties of a family of Ca2+-binding proteins with 4 or 3 EF-hand motifs have been studied with desensitized skinned fiber preparations. Proteins with 4 EF hands (such as troponins C - TnCs) are dumb-bell shaped, those with 3 EF hands (parvalbumin) being ellipsoidal. The number of active sites varied between four and two. We find that the ability to anchor in the fiber is limited to proteins with 4 EF hands and, at least, two active Ca2+-binding sites, one each in the N- and C-termini. The results suggest that the dumb-bell shaped global structure is critical for the switching action in muscular contraction, and a trigger site in the N-terminus and a structural site in the C-terminus need to be active in order to regulate contractility.
Babu
A
A
Albert Einstein College of Medicine, Bronx, NY 10461.
Lehman
W
W
Gulati
J
J
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology; D006224:Cricetinae; D046911:Macromolecular Substances; D008647:Mesocricetus; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010320:Parvalbumins / Q000502:physiology; D011487:Protein Conformation; D011817:Rabbits; D013324:Strontium / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014336:Troponin / Q000502:physiology; D019209:Troponin C
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D046911:Macromolecular Substances; D010320:Parvalbumins; D014336:Troponin; D019209:Troponin C; C034733:oncomodulin; D002118:Calcium; D013324:Strontium