title: Interaction of troponin I and troponin C. Use of the two-dimensional nuclear magnetic resonance transferred nuclear Overhauser effect to determine the structure of the inhibitory troponin I peptide when bound to skeletal troponin C.
abstract: We have used two-dimensional 1H nuclear magnetic resonance spectroscopy to determine the structure of the synthetic inhibitory peptide N alpha-acetyl TnI(104-115) amide bound to calcium-saturated skeletal troponin C (TnC). Conformational changes in the peptide induced by the formation of the troponin I (TnI) peptide-TnC complex were followed by the study of the transferred nuclear Overhauser effect, a technique that allows one to determine the structure of a ligand bound to a macromolecule. The structure of the bound TnI peptide reveals an amphiphilic alpha-helix, distorted around the two central proline residues. The central bend in the peptide functions to bring the residues on the hydrophobic face into closer proximity with each other, thereby forming a small hydrophobic pocket. The hydrophilic, basic residues extend off the opposite face of the peptide. Hydrophobic surfaces on TnC that become exposed upon binding of calcium are involved in the binding of the TnI peptide, but electrostatic interactions also contribute to the strength of the interaction. The role of amphiphilic helices in the targeting of calcium-binding proteins such as troponin C will be discussed.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Canada.
authors.forename: A P
authors.initials: AP
authors.lastname: Campbell
authors.forename: B D
authors.initials: BD
authors.lastname: Sykes
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D013237:Stereoisomerism; D014336:Troponin / Q000737:chemistry / Q000378:metabolism*; D019209:Troponin C; D019210:Troponin I; D014422:Turkeys
chemical_list: D008024:Ligands; D010455:Peptides; D014336:Troponin; D019209:Troponin C; D019210:Troponin I; D002118:Calcium