Light-induced structural changes in a short light, oxygen, voltage (LOV) protein revealed by molecular dynamics simulations—implications for the understanding of LOV photoactivation

摘要: The modularity of light, oxygen, voltage (LOV) blue-light photoreceptors has recently been exploited for the design LOV-based optogenetic tools, which allow light-dependent control biological functions. For understanding LOV sensory function and hence optimal optogentic tools it is essential to gain an in depth atomic-level underlying photoactivation intramolecular signal-relay mechanisms. To address this question we performed molecular dynamics simulations on both dark- light-adapted state PpSB1-LOV, a short dimeric bacterial LOV-photoreceptor protein, crystallized under constant illumination. While dimers remained globally stable during light-state simulation with regard Jα coiled-coil, distinct conformational changes glutamine vicinity FMN chromophore are observed. In contrast, multiple Jα-helix conformations sampled dark-state. These coincide displacement Iβ Hβ strands relative structure result correlated rotation core domains dimer. global most likely initiated by reorientation conserved Q116, whose side chain flips between Aβ (dark state) strand (light state), while maintaining two potential hydrogen bonds FMN-N5 FMN-O4, respectively. This local Q116-FMN impacts inter-subunit salt-bridge (K117-E96), stabilized light state, accounting observed decreased mobility. Based these findings propose alternative mechanism signal-relay, assigning structural role “flipping” glutamine. proposed discussed universal applicability its implications tools.