title: The structure of Lethocerus troponin C: insights into the mechanism of stretch activation in muscles.
abstract: To gain a molecular description of how muscles can be activated by mechanical stretch, we have solved the structure of the calcium-loaded F1 isoform of troponin C (TnC) from Lethocerus and characterized its interactions with troponin I (TnI). We show that the presence of only one calcium cation in the fourth EF hand motif is sufficient to induce an open conformation in the C-terminal lobe of F1 TnC, in contrast with what is observed in vertebrate muscle. This lobe interacts in a calcium-independent way both with the N terminus of TnI and, with lower affinity, with a region of TnI equivalent to the switch and inhibitory peptides of vertebrate muscles. Using both synthetic peptides and recombinant proteins, we show that the N lobe of F1 TnC is not engaged in interactions with TnI, excluding a regulatory role of this domain. These findings provide insights into mechanically stimulated muscle contraction.
authors.affiliation: Molecular Structure Division, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
authors.forename: Gianfelice
authors.initials: G
authors.lastname: De Nicola
authors.forename: Christoph
authors.initials: C
authors.lastname: Burkart
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: Bogos
authors.initials: B
authors.lastname: Agianian
authors.forename: Siegfried
authors.initials: S
authors.lastname: Labeit
authors.forename: Stephen
authors.initials: S
authors.lastname: Martin
authors.forename: Belinda
authors.initials: B
authors.lastname: Bullard
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005426:Flight, Animal; D020062:Heteroptera / Q000378:metabolism* / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D009132:Muscles / Q000502:physiology; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D019209:Troponin C / Q000737:chemistry* / Q000502:physiology
chemical_list: D020033:Protein Isoforms; D019209:Troponin C; D002118:Calcium