Dynamics of Conformational Changes of Arabidopsis Phototropin 1 LOV2 with the Linker Domain

Nakasone, Yusuke; Eitoku, Takeshi; Matsuoka, Daisuke; Tokutomi, Satoru; Terazima, Masahide

doi:10.1016/j.jmb.2006.12.074

Cited by 84 publications

(176 citation statements)

References 45 publications

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“…Finally, from 330 μs. This can be correlated with the experimental time range of 300 μs-1 ms for these events, determined by Nakasone et al 19 for the LOV2 domain of phototropin1 from Arabidopsis using transient-grating methods. Thus, we conclude from the previous investigation that the KMC-MD method reproduces the multiscale relaxation behavior of the AsLOV2-Jα system after CFN-adduct formation reliably and permits to extend the computationally accessible simulation times to experimental timescales.…”

Section: Resultssupporting

confidence: 79%

“…8 excitation. 19 In their paper, they speculated that complete unfolding of the Jα-helix takes place after cleavage from the LOV2 core. To investigate the detachment and subsequent unfolding process of the Jα-helix in more detail, we visualize in Figs.…”

Section: Resultsmentioning

confidence: 99%

“…18 However, since its range of applicability for small proteins usually spans from nanoseconds up to sub-microseconds, its usefulness to study signaling processes on typical experimental timescales is only limited. 19 In order to reach longer timescales with the MD technique, several approaches have been proposed in the past decades. One of those is the coarse-graining (CG) approach, in which the system's degrees of freedom and, thus, the number of interactions is reduced enabling the use of larger time steps at lower computational costs.…”

Section: Introductionmentioning

confidence: 99%

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A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

Peter

Dick

Baeurle

2012

The Journal of Chemical Physics

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Signal proteins are able to adapt their response to a change in the environment, governing in this way a broad variety of important cellular processes in living systems. While conventional moleculardynamics (MD) techniques can be used to explore the early signaling pathway of these protein systems at atomistic resolution, the high computational costs limit their usefulness for the elucidation of the multiscale transduction dynamics of most signaling processes, occurring on experimental timescales. To cope with the problem, we present in this paper a novel multiscale-modeling method, based on a combination of the kinetic Monte-Carlo-and MD-technique, and demonstrate its suitability for investigating the signaling behavior of the photoswitch light-oxygen-voltage-2-Jα domain from Avena Sativa (AsLOV2-Jα) and an AsLOV2-Jα-regulated photoactivable Rac1-GTPase (PA-Rac1), recently employed to control the motility of cancer cells through light stimulus. More specifically, we show that their signaling pathways begin with a residual re-arrangement and subsequent H-bond formation of amino acids near to the flavin-mononucleotide chromophore, causing a coupling between β-strands and subsequent detachment of a peripheral α-helix from the AsLOV2-domain. In the case of the PA-Rac1 system we find that this latter process induces the release of the AsLOV2-inhibitor from the switchII-activation site of the GTPase, enabling signal activation through effector-protein binding. These applications demonstrate that our approach reliably reproduces the signaling pathways of complex signal proteins, ranging from nanoseconds up to seconds at affordable computational costs.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

Peter

Dick

Baeurle

2012

The Journal of Chemical Physics

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“…This effect was attributed to the transformation from α-helix to an unfolded loop causing an increase in friction with the solvent, manifested by the D decrease correlating with the extent of the unfolding. 17 Similarly, D decreases were observed during the photocycles of photosensor proteins (e.g., light-oxygen-voltage domain and photoactive yellow protein) and are ascribable to conformational changes of the α-helices, because truncation of the helices eliminated the change in D. 18,19 Furthermore, conformational changes of an α-helix upon light activation of a light-oxygen-voltage domain of phototropin have been shown by heteronuclear single quantum coherence NMR spectra to entail unfolding of the helix. 20 Given the analogy, AS-1 and AS-2 helices in the HAMP of NpHtrII might also undergo unfolding, upon which backbone carbonyl and NH groups become available for forming hydrogen bonds with the surrounding water molecules, providing greater friction with the aqueous solvent.…”

Section: Discussionmentioning

confidence: 97%

Signal Transmission through the HtrII Transducer Alters the Interaction of Two α-Helices in the HAMP Domain

Inoue

Sasaki

Spudich

et al. 2008

Journal of Molecular Biology

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“…be the primary step necessary for the activation of STK (18). Under BL irradiation, the J␣-helix unfolds, and then its interaction with the ␣/␤-scaffold would change (13,(25)(26)(27).…”

Section: Phototropin (Phot)mentioning

confidence: 99%

Blue Light-excited Light-Oxygen-Voltage-sensing Domain 2 (LOV2) Triggers a Rearrangement of the Kinase Domain to Induce Phosphorylation Activity in Arabidopsis Phototropin1

Oide

Okajima

Kashojiya

et al. 2016

Journal of Biological Chemistry

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Phototropin1 is a blue light (BL) receptor in plants and shows BL-dependent kinase activation. The BL-excited light-oxygenvoltage-sensing domain 2 (LOV2) is primarily responsible for the activation of the kinase domain; however, the molecular mechanism by which conformational changes in LOV2 are transmitted to the kinase domain remains unclear. Here, we investigated BL-induced structural changes of a minimum functional fragment of Arabidopsis phototropin1 composed of LOV2, the kinase domain, and a linker connecting the two domains using small-angle x-ray scattering (SAXS). The fragment existed as a dimer and displayed photoreversible SAXS changes reflected in the radii of gyration of 42.9 Å in the dark and 48.8 Å under BL irradiation. In the dark, the molecular shape reconstructed from the SAXS profiles appeared as two bean-shaped lobes in a twisted arrangement that was 170 Å long, 80 Å wide, and 50 Å thick. The molecular shape under BL became slightly elongated from that in the dark. By fitting the crystal structure of the LOV2 dimer and a homology model of the kinase domain to their inferred shapes, the BL-dependent change could be interpreted as the positional shift in the kinase domain relative to that of the LOV2 dimer. In addition, we found that lysine 475, a functionally important residue, in the N-terminal region of LOV2 plays a critical role in transmitting the structural changes in LOV2 to the kinase domain. The interface between the domains is critical for signaling, suitably changing the structure to activate the kinase in response to conformational changes in the adjoining LOV2. Phototropin (phot)2 is one of the blue light (BL) receptor proteins in plants (1, 2). It plays several important roles to maximize the efficiency of photosynthesis: namely phototropism (3), chloroplast movement (4, 5), stomata opening (6), and leaf expansion (7). Most plants possess two isoforms of phot, designated as phot1 and phot2 (1). Both isoforms redundantly regulate stomata opening (6) and chloroplast accumulation depending on fluence rate of BL (3). However, only phot2 is responsible for the photoavoidance response in chloroplast relocation (4). Regarding the phototropic response, phot2 works under high irradiance condition, whereas phot1 predominantly initiates the response under low irradiance condition (3).The structure of plant phot, which consists of ϳ950 -1000 amino acid residues and two flavin mononucleotide (FMN) molecules (1), folds into three functional domains (Fig. 1A). The N-terminal half contains two light-oxygen-voltage-sensing domains (LOVs) (designated LOV1 and LOV2) (8, 9), which belong to the PAS (Per-Arnt-Sim) superfamily found in heterodimeric interaction in cellular signaling. Each LOV domain receives BL via the FMN molecule bound to the pocket formed by the characteristic ␣-helix/␤-strand-mixed structure known as the ␣/␤-scaffold (10, 11). The C-terminal half of phot is a serine-threonine kinase (STK) domain classified into group VIII of the AGC family (12). The linker region, which has J␣-heli...

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Dynamics of Conformational Changes of Arabidopsis Phototropin 1 LOV2 with the Linker Domain

Cited by 84 publications

References 45 publications

A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

A novel computer simulation method for simulating the multiscale transduction dynamics of signal proteins

Signal Transmission through the HtrII Transducer Alters the Interaction of Two α-Helices in the HAMP Domain

Blue Light-excited Light-Oxygen-Voltage-sensing Domain 2 (LOV2) Triggers a Rearrangement of the Kinase Domain to Induce Phosphorylation Activity in Arabidopsis Phototropin1

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