Pope, M. | bioRxiv Science

bioRxiv2022

Light activation of Orange Carotenoid Protein reveals initial C8'-C7' double bond trans/cis photoisomerization

Orange Carotenoid protein (OCP) is the only known photoreceptor which uses carotenoid for its activation. It is found exclusively in cyanobacteria, where it functions to control light-harvesting of the photosynthetic machinery. However, the photochemical reactions and structural dynamics of this unique photosensing process are not yet resolved. We present time-resolved crystal structures at second-to-minute delays under bright illumination, capturing the early photoproduct and structures of the subsequent reaction intermediates. The first stable photoproduct shows concerted isomerization of C9-C8 and C7-C6 single bonds in the bicycle-pedal (BP) manner and structural changes in the N-terminal domain with minute timescale kinetics. These are followed by a thermally-driven recovery of the BP isomer to the dark state carotenoid configuration. Structural changes propagate to the C-terminal domain, resulting, at later time, in the H-bond rupture of the carotenoid keto group with protein residues. The isomerization and its transient nature are confirmed in OCP crystals and solution by FTIR and UV/Vis spectroscopy. This study reveals the single bond isomerization of the carotenoid in the BP manner and subsequent thermal structural reactions as the basis of OCP photoreception. Understanding and potentially controlling the OCP dynamics offers the prospect of novel applications in biomass engineering as well as in optogenetics and bioimaging.

biophysics↗

bioRxiv2021

Modular origins of high-amplitude co-fluctuations in fine-scale functional connectivity dynamics

The topology of structural brain networks shapes brain dynamics, including the correlation structure of brain activity (functional connectivity) as estimated from functional neuroimaging data. Empirical studies have shown that functional connectivity fluctuates over time, exhibiting patterns that vary in the spatial arrangement of correlations among segregated functional systems. Recently, an exact decomposition of functional connectivity into frame-wise contributions has revealed fine-scale dynamics that are punctuated by brief and intermittent episodes (events) of high-amplitude co-fluctuations involving large sets of brain regions. Their origin is currently unclear. Here, we demonstrate that similar episodes readily appear in silico using computational simulations of whole-brain dynamics. As in empirical data, simulated events contribute disproportionately to long-time functional connectivity, involve recurrence of patterned co-fluctuations, and can be clustered into distinct families. Importantly, comparison of event-related patterns of co-fluctuations to underlying patterns of structural connectivity reveals that modular organization present in the coupling matrix shape patterns of event-related co-fluctuations. Our work suggests that brief, intermittent events in functional dynamics are partly shaped by modular organization of structural connectivity. Significance StatementBrain regions engage in complex patterns of activation and co-activation over time. Relating these patterns to rest or task-related neural processing is a central challenge in cognitive neuroscience. Recent work has identified brief intermittent bursts of brain-wide signal co-fluctuations, called events, and shown that events drive functional connectivity. The origins of events are still unclear. Here, we address this gap in knowledge by implementing computational models of neural oscillators coupled by anatomical connections derived from maps of the human cerebral cortex. Analysis of the emerging large-scale brain dynamics reveals brief episodes with high system-wide signal amplitudes. Simulated events closely correspond to those seen recently in empirical recordings. Notably, simulated events are significantly aligned with underlying structural modules, thus suggesting an important role of modular network organization.

neuroscience↗