Dimeric allostery mechanism of the plant circadian clock photoreceptor ZEITLUPE

Abstract

In Arabidopsis thaliana, the Light-Oxygen-Voltage (LOV) domain containing protein ZEITLUPE (ZTL) integrates light quality, intensity, and duration into regulation of the circadian clock. Recent structural and biochemical studies of ZTL indicate that the protein diverges from other members of the LOV superfamily in its allosteric mechanism, and that the divergent allosteric mechanism hinges upon conservation of two signaling residues G46 and V48 that alter dynamic motions of a Gln residue implicated in signal transduction in all LOV proteins. Here, we delineate the allosteric mechanism of ZTL via an integrated computational approach that employs atomistic simulations of wild type and allosteric variants of ZTL in the functional dark and light states, together with Markov state and supervised machine learning classification models. This approach has unveiled key factors of the ZTL allosteric mechanisms, and identified specific interactions and residues implicated in functional allosteric changes. The final results reveal atomic level insights into allosteric mechanisms of ZTL function that operate via a non-trivial combination of population-shift and dynamics-driven allosteric pathways.

Dynamics of hydrogen bonds in the secondary structures of allosteric protein Avena Sativa phototropin 1

“…Following previous studies using this strategy [24] , [25] , two transient states were constructed and subjected to simulations as the following to explore As LOV2 conformational space and dynamical properties coupled with the transitions between its dark and light states. To mimic As LOV2 in the moment when its dark state is excited by the blue light with photo-induced covalent bond and before conformational transition to its light state structure, the transient light state could be constructed by forming the photo-induced covalent bond in the As LOV2 dark state structure ( Fig.…”

Elevator-type Mechanism of the Cyanobacterial Bicarbonate Transporter

“…25,26 Recent efforts in Markov state modeling have characterized the conformational heterogeneity of proteins of key interest to the plant biology community including phytohormone receptors, [27][28][29] and circadian clock photoreceptors. [30][31][32] Several membrane transporters have also been investigated using these methodologies including sugar transporters (SWEETs and SemiSWEETs), [33][34][35] bacterial nitrate transporters, 36 human neurotransmitter 26,37 and peptide transporters. 38 However, these transporters follow either the rocker-switch or rocking bundle mechanisms of alternate-access to facilitate the substrate transport.…”