Inhibition of mutant troponin C activity by an intra-domain disulphide bond.
Triggering of contraction in striated muscles involves a conformational transition in the N-terminal domain of troponin C, the calcium-binding component of thin filaments. We have designed a mutant troponin C in which the key conformational transition and the calcium-regulatory activity are reversibly blocked by the formation of a disulphide bridge. Our results may be applicable to other proteins of the same family of calcium-binding proteins.
Grabarek
Z
Z
Department of Muscle Research, Boston Biomedical Research Institute, Massachusetts 02114.
Tan
R Y
RY
Wang
J
J
Tao
T
T
Gergely
J
J
D000818:Animals; D001388:Aziridines; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D003460:Crystallization; D003619:Dansyl Compounds; D004220:Disulfides; D004229:Dithiothreitol / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005456:Fluorescent Dyes; D009119:Muscle Contraction; D009154:Mutation; D011487:Protein Conformation; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014336:Troponin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019209:Troponin C; D019210:Troponin I; D020107:Troponin T; D014443:Tyrosine
D001388:Aziridines; D003619:Dansyl Compounds; D004220:Disulfides; D005456:Fluorescent Dyes; D014336:Troponin; D019209:Troponin C; D019210:Troponin I; D020107:Troponin T; D014443:Tyrosine; C017173:dansylaziridine; D004492:Edetic Acid; D002118:Calcium; D004229:Dithiothreitol