Signaling mechanisms of LOV domains

new insights from molecular dynamics studies.

Peter L. Freddolino, Kevin H. Gardner, Klaus Schulten

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1158-1170
Number of pages13
JournalPhotochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology
Volume12
Issue number7
StatePublished - Jul 2013

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Molecular Dynamics Simulation
Phototropins
Molecular dynamics
Oxygen
molecular dynamics
helices
Light
Electric potential
electric potential
oxygen
adducts
Plant Photoreceptors
dissociation
glutamine
photoreceptors
cysteine
algae
Algae
Glutamine
Cysteine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Signaling mechanisms of LOV domains: new insights from molecular dynamics studies.",
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.",
author = "Freddolino, {Peter L.} and Gardner, {Kevin H.} and Klaus Schulten",
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AU - Gardner, Kevin H.

AU - Schulten, Klaus

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N2 - 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.

AB - 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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