Why BLUF photoreceptors with roseoflavincofactors lose their biological functionality

Merz, Thomas; Sadeghian, Keyarash; Schütz, Martin

doi:10.1039/c1cp21386e

Cited by 15 publications

(22 citation statements)

References 54 publications

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“…The flavin receives a proton as well as an electron when excited, and Gln-48 Ne1 is found to move slightly from the N5 atom of FMN on photoactivation of OaPAC (dark state 3.16 Å, active 3.53 Å). This shift suggests that the glutamine receives a proton from the tyrosine and loses one to the flavin, giving the tautomeric (imidic) form suggested by spectroscopic and computational analyses, but requiring only very modest sidechain rotation (15,18,27,28,(33)(34)(35). The hydrogen bonding pattern around the flavin may change as shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of photoactivation of a light-regulated adenylate cyclase

Ohki

Sato‐Tomita

Matsunaga

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The photoactivated adenylate cyclase (PAC) from the photosynthetic cyanobacterium Oscillatoria acuminata (OaPAC) detects light through a flavin chromophore within the N-terminal BLUF domain. BLUF domains have been found in a number of different light-activated proteins, but with different relative orientations. The two BLUF domains of OaPAC are found in close contact with each other, forming a coiled coil at their interface. Crystallization does not impede the activity switching of the enzyme, but flash cooling the crystals to cryogenic temperatures prevents the signature spectral changes that occur on photoactivation/deactivation. High-resolution crystallographic analysis of OaPAC in the fully activated state has been achieved by cryocooling the crystals immediately after light exposure. Comparison of the isomorphous light-and dark-state structures shows that the active site undergoes minimal changes, yet enzyme activity may increase up to 50-fold, depending on conditions. The OaPAC models will assist the development of simple, direct means to raise the cyclic AMP levels of living cells by light, and other tools for optogenetics.cAMP | BLUF domain | optogenetics | photoactivation | allostery

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Section: Discussionmentioning

confidence: 99%

Molecular mechanism of photoactivation of a light-regulated adenylate cyclase

Ohki

Sato‐Tomita

Matsunaga

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…As no standard force field parameters for iGln63 are available, reported models of BLUF domains with iGln63 mostly rely on QM cluster or QM/MM approaches with iGln63 in the QM part (Domratcheva et al, 2008 ; Sadeghian et al, 2008 , 2010 ; Khrenova et al, 2010 , 2011b ; Udvarhelyi and Domratcheva, 2011 ). Merz et al ( 2011 ) technically belongs to that group as well, but investigates the effect of a FMN replacement by roseoflavin, and will therefore not be discussed further. Most photocycle studies discuss the Trp-in/Trp-out problem to some extent, but all presented models assume Trp-out (PDB ID 2IYG) to be the resting state, and Trp-in is disregarded as a resting state candidate by initial comparison of structural and experimental data.…”

Section: Computational Studies On Blufmentioning

confidence: 99%

A proposal for a dipole-generated BLUF domain mechanism

Mathes

Götze

2015

Front. Mol. Biosci.

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The resting and signaling structures of the blue-light sensing using flavin (BLUF) photoreceptor domains are still controversially debated due to differences in the molecular models obtained by crystal and NMR structures. Photocycles for the given preferred structural framework have been established, but a unifying picture combining experiment and theory remains elusive. We summarize present work on the AppA BLUF domain from both experiment and theory. We focus on IR and UV/vis spectra, and to what extent theory was able to reproduce experimental data and predict the structural changes upon formation of the signaling state. We find that the experimental observables can be theoretically reproduced employing any structural model, as long as the orientation of the signaling essential Gln63 and its tautomer state are a choice of the modeler. We also observe that few approaches are comparative, e.g., by considering all structures in the same context. Based on recent experimental findings and a few basic calculations, we suggest the possibility for a BLUF activation mechanism that only relies on electron transfer and its effect on the local electrostatics, not requiring an associated proton transfer. In this regard, we investigate the impact of dispersion correction on the interaction energies arising from weakly bound amino acids.

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“…Therefore, one should also consider that the tyrosine/isoalloxazine orientation might have been changed in disfavour of electron transfer due to the additional, more bulky dimethylamino group of roseoflavin. In a recent theoretical work, Merz and co-workers found that the fluorescence-quenching behaviour in the protein would be, indeed, supported by a TICT mechanism; however, the loss of photoactivation may rather be due to a missing low-lying conical intersection between the locally excited state energy surface and the tyrosine/flavin charge transfer state surface [ 93 ].…”

Section: Photoinduced Electron Transfer In Bluf Domains: Redox Tuningmentioning

confidence: 99%

Molecular eyes: proteins that transform light into biological information

2013

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Most biological photoreceptors are protein/cofactor complexes that induce a physiological reaction upon absorption of a photon. Therefore, these proteins represent signal converters that translate light into biological information. Researchers use this property to stimulate and study various biochemical processes conveniently and non-invasively by the application of light, an approach known as optogenetics. Here, we summarize the recent experimental progress on the family of blue light receptors using FAD (BLUF) receptors. Several BLUF photoreceptors modulate second messenger levels and thus represent highly interesting tools for optogenetic application. In order to activate a coupled effector protein, the flavin-binding pocket of the BLUF domain undergoes a subtle rearrangement of the hydrogen network upon blue light absorption. The hydrogen bond switch is facilitated by the ultrafast light-induced proton-coupled electron transfer (PCET) between a tyrosine and the flavin in less than a nanosecond and remains stable on a long enough timescale for biochemical reactions to take place. The cyclic nature of the photoinduced reaction makes BLUF domains powerful model systems to study protein/cofactor interaction, protein-modulated PCET and novel mechanisms of biological signalling. The ultrafast nature of the photoconversion as well as the subtle structural rearrangement requires sophisticated spectroscopic and molecular biological methods to study and understand this highly intriguing signalling process.

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Why BLUF photoreceptors with roseoflavincofactors lose their biological functionality

Cited by 15 publications

References 54 publications

Molecular mechanism of photoactivation of a light-regulated adenylate cyclase

Molecular mechanism of photoactivation of a light-regulated adenylate cyclase

A proposal for a dipole-generated BLUF domain mechanism

Molecular eyes: proteins that transform light into biological information

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