The Use of Peptide Mimetics to Define the Actin-Binding Sites on the Head of the Myosin Molecule
Definition of the molecular mechanisms in muscle contraction and its regulation entails a description of how the components of the organised assembly of proteins first dock with their substrates/partners, then interact and transmit information through the molecular array. Crosslinking studies and experiments with proteolysed fragments of the myosin head (subfragment 1, S1) from a variety of laboratories [e.g. Chaussepied et al., 1986a; Sutoh, 1983] have indicated the approximate regions of the molecule involved in complex formation. In order to define precisely the exact locations of these interfaces we have synthesized peptides based on the S1 sequence and tested these for their ability to bind to actin and influence its biological properties. Such chemical synthesis allows small regions of the parent protein, usually not obtainable by proteolytic or chemical digestion, to be examined in isolation.
KeywordsHPLC Cysteine Thiol Dipeptide Dock
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- Bhandari, D.G., Levine, B.A., Trayer, I.P. & Yeadon, M.E. (1986) 1H-NMR study of mobility and conf irmational constraints within the proline-rich N-terminal of the LCl alkaline light chain of skeletal myosin. Correlation with similar segments in other protein systems. Eur. J. Biochem. 160: 349–356.PubMedCrossRefGoogle Scholar
- Grand, R.J.A. (1982) The structure and function of myosin light chains. Life Sci. Reports, 1: 105–160.Google Scholar
- Grand, R.J.A., Henry, G.D., Moir, A., Perry, S.V., Trayer, I.P., Dalgarno, D.C., Levine, B.A. & Parker, S.B. (1983) Modulation by troponin-C of the troponin-I inhibition of skeletal actomyosin interaction. A PMR spectral study. In de Bernard, B., Sottocasa, G.L., Sandri, G., Carafoli, E., Taylor, A.N., Vanaman, T.C. & Williams, R.J.P. (eds): Calcium-binding proteins, 1983. Elsevier Science Publishers, Amsterdam, pp 379–380.Google Scholar
- Kraft, Th., Trayer, I.P. & Brenner, B. (1991) Myosin peptides and cross-bridge kinetics. In Rüegg, J.C. (ed): Peptides as probes in muscle research. Springer-Verlag, Heidelberg, (this volume).Google Scholar
- Levine, B.A., Moir, A.J.G., Trayer, I.P. & Williams, R.J.P. (1990) Nuclear magnetic resonance studies of calcium modulated proteins and actin-myosin interaction. In Squire, J. (ed): Molecular mechanisms in muscle contraction. McMillan Press, London, pp 171–209.Google Scholar
- Moir, A.J.G., Levine, B.A., Goodearl, A.J. & Trayer, I.P. (1987) The interaction of actin with myosin subfragment 1 and with pPDM-crosslinked S1: a 1H-NMR investigation. J. Muscle Res. & Cell Motil. 8: 68–69.Google Scholar
- Rüegg, J.C., Van Eyk, J., Hodges, R. & Trayer, I.P. (1991) Myosin and troponin peptides affecting Ca -sensitivity of skinned fibres. In Rüegg, J.C. (ed): Peptides as probes in muscle research. Springer-Verlag, Heidelberg, (this volume).Google Scholar