title: Versatile cardiac troponin chimera for muscle protein structural biology and drug discovery.
abstract: Investigation of the molecular interactions within and between subunits of the heterotrimeric troponin complex, and with other proteins in the sarcomere, has revealed salient structural elements involved in regulation of muscle contraction. The discovery of new cardiotonic drugs and structural studies utilizing intact troponin, or regulatory complexes formed between the key regions identified in troponin C and troponin I, face intrinsic and technical difficulties associated with weak protein-protein interactions and with solubility, aggregation, stability of the overall architecture, isotope labeling, and size, respectively. We have designed and characterized a chimeric troponin C-troponin I hybrid protein with a cleavable linker that is useful for producing isotopically labeled troponin peptides, stabilizes their interaction, and has proven to be a faithful representation of the original complex in the systolic state, but lacking its disadvantages, making it particularly suitable for drug screening and structural studies.
authors.affiliation: Department of Biochemistry, University of Alberta , 4-19 Medical Sciences Building, Edmonton, Alberta Canada , T6G 2H7.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Pineda-Sanabria
authors.forename: Olivier
authors.initials: O
authors.lastname: Julien
authors.forename: Brian D
authors.initials: BD
authors.lastname: Sykes
mesh_terms: D015764:Bepridil / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D055808:Drug Discovery; D019906:Nuclear Magnetic Resonance, Biomolecular; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000378:metabolism; D013917:Thrombin / Q000737:chemistry; D019209:Troponin C / Q000737:chemistry*; D019210:Troponin I / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D011994:Recombinant Proteins; D013449:Sulfonamides; D019209:Troponin C; D019210:Troponin I; C017967:W 7; D015764:Bepridil; D013917:Thrombin; D002118:Calcium