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Signaling mechanisms of LOV domains: new insights from molecular dynamics studies

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Abstract

Phototropins are one of several classes of photoreceptors used by plants and algae to respond to light. These proteins contain flavin-binding LOV (Light-Oxygen-Voltage) domains that form covalent cysteine- flavin adducts upon exposure to blue light, leading to the enhancement of phototropin kinase activity. Several lines of evidence suggest that adduct formation in the phototropin LOV2 domains leads to the dissociation of an alpha helix (Jα) from these domains as part of the light-induced activation process. However, crystal structures of LOV domains both in the presence and absence of the Jα helix show very few differences between dark and illuminated states, and thus the precise mechanism through which adduct formation triggers helical dissociation remains poorly understood. Using Avena sativa phototropin 1 LOV2 as a model system, we have studied the interactions of the LOV domain core with the Jα helix through a series of equilibrium molecular dynamics simulations. Here we show that conformational transitions of a conserved glutamine residue in the flavin binding pocket are coupled to altered dynamics of the Jα helix both through a shift in dynamics of the main β-sheet of the LOV domain core and through a secondary pathway involving the N-terminal A′α helix.

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Authors and Affiliations

  1. Joint Centers for Systems Biology, Columbia University, New York, NY, USA

    Peter L. Freddolino

  2. Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Kevin H. Gardner

  3. Beckman Institute and Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Klaus Schulten

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  1. Peter L. Freddolino
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  2. Kevin H. Gardner
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  3. Klaus Schulten
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Correspondence to Kevin H. Gardner or Klaus Schulten.

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† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3pp25400c

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Freddolino, P.L., Gardner, K.H. & Schulten, K. Signaling mechanisms of LOV domains: new insights from molecular dynamics studies. Photochem Photobiol Sci 12, 1158–1170 (2013). https://doi.org/10.1039/c3pp25400c

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