Blue light using flavin (BLUF) photoreceptor proteins play a vital role in a wide range of light-regulated processes. In the BLUF domain Slr1694, the photocycle involves a photoinduced proton-coupled electron transfer (PCET) reaction, making it a prototypical model system for studying photoinduced PCET in proteins. Experimentally, photoexcitation of the flavin induces electron transfer from a nearby tyrosine to the flavin. The formation of this charge-transfer state induces proton transfer along a proton relay involving double proton transfer from the tyrosine to the flavin, mediated by a connecting glutamine. Free energy simulations indicate that photoexcitation of the flavin induces the formation of the proton relay if it is not already formed. Electrostatically embedded time-dependent density functional theory (TDDFT) calculations indicate that although the charge transfer state is higher in energy than the locally excited flavin state prior to photoexcitation, the protein environment can reorganize in a manner that reduces the energy gap between these two states, enabling electron transfer to the flavin. An electrostatic analysis identifies motions of individual residues, such as arginine, that stabilize electron transfer from tyrosine to the flavin. Multireference wavefunction calculations illustrate that double proton transfer along the proton relay becomes energetically favorable only in the charge-transfer state. The interplay between electrostatics and conformational changes facilitates the critical PCET reaction in the BLUF photocycle, which leads to long-range signaling that has applications in optogenetics and biosensors.<br/>

Impact of protein conformational changes and electrostatics on a BLUF photoreceptor

2019 Fall National Meeting

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