title: Toward Understanding the Molecular Bases of Stretch Activation: A STRUCTURAL COMPARISON OF THE TWO TROPONIN C ISOFORMS OF LETHOCERUS.
abstract: Muscles are usually activated by calcium binding to the calcium sensory protein troponin-C, which is one of the three components of the troponin complex. However, in cardiac and insect flight muscle activation is also produced by mechanical stress. Little is known about the molecular bases of this calcium-independent activation. In Lethocerus, a giant water bug often used as a model system because of its large muscle fibers, there are two troponin-C isoforms, called F1 and F2, that have distinct roles in activating the muscle. It has been suggested that this can be explained either by differences in structural features or by differences in the interactions with other proteins. Here we have compared the structural and dynamic properties of the two proteins and shown how they differ. We have also mapped the interactions of the F2 isoform with peptides spanning the sequence of its natural partner, troponin-I. Our data have allowed us to build a model of the troponin complex and may eventually help in understanding the specialized function of the F1 and F2 isoforms and the molecular mechanism of stretch activation.
authors.affiliation: From the Department of Clinical and Basic Neurosciences, Wohl Institute, King's College, London SE5 3RT, United Kingdom.
authors.forename: Domenico
authors.initials: D
authors.lastname: Sanfelice
authors.affiliation: the Department of Life Sciences, Imperial College, London SW7 2AZ, United Kingdom.
authors.forename: Máximo
authors.initials: M
authors.lastname: Sanz-Hernández
authors.affiliation: the Department of Life Sciences, Imperial College, London SW7 2AZ, United Kingdom.
authors.forename: Alfonso
authors.initials: A
authors.lastname: de Simone
authors.affiliation: the Department of Biology, University of York, York YO10 5DD, United Kingdom, and.
authors.forename: Belinda
authors.initials: B
authors.lastname: Bullard
authors.affiliation: From the Department of Clinical and Basic Neurosciences, Wohl Institute, King's College, London SE5 3RT, United Kingdom, the Department of Molecular Medicine, Universita' of Pavia, Pavia I27100, Italy annalisa.1.pastore@kcl.ac.uk.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
mesh_terms: D000818:Animals; D020062:Heteroptera / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D019209:Troponin C / Q000235:genetics / Q000378:metabolism*
chemical_list: D019476:Insect Proteins; D020033:Protein Isoforms; D019209:Troponin C
keywords: muscle; protein-protein interaction; stress; structural biology; structure-function