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    A coupled equilibrium shift mechanism in Calmodulin-Mediated signal transduction

    Gsponer, J. and Christodoulou, John and Cavalli, A. and Bui, J.M. and Richter, B. and Dobson, C.M. and Vendruscolo, M. (2008) A coupled equilibrium shift mechanism in Calmodulin-Mediated signal transduction. Structure 16 (5), pp. 736-746. ISSN 0969-2126.

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    Abstract

    We used nuclear magnetic resonance data to determine ensembles of conformations representing the structure and dynamics of calmodulin (CaM) in the calcium-bound state (Ca2+-CaM) and in the state bound to myosin light chain kinase (CaM-MLCK). These ensembles reveal that the Ca2+-CaM state includes a range of structures similar to those present when CaM is bound to MLCK. Detailed analysis of the ensembles demonstrates that correlated motions within the Ca2+-CaM state direct the structural fluctuations toward complex-like substates. This phenomenon enables initial ligation of MLCK at the C-terminal domain of CaM and induces a population shift among the substates accessible to the N-terminal domain, thus giving rise to the cooperativity associated with binding. Based on these results and the combination of modern free energy landscape theory with classical allostery models, we suggest that a coupled equilibrium shift mechanism controls the efficient binding of CaM to a wide range of ligands.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 04 Aug 2010 14:09
    Last Modified: 02 Aug 2023 16:49
    URI: https://eprints.bbk.ac.uk/id/eprint/1004

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