Signaling and Adaptation Modulate the Dynamics of the Photosensoric Complex of Natronomonas pharaonis

Motile bacteria and archaea respond to chemical and physical stimuli seeking optimal conditions for survival. To this end transmembrane chemo- and photoreceptors organized in large arrays initiate signaling cascades and ultimately regulate the rotation of flagellar motors. To unravel the molecular mechanism of signaling in an archaeal phototaxis complex we performed coarse-grained molecular dynamics simulations of a trimer of receptor/transducer dimers, namely NpSRII/NpHtrII from Natronomonas pharaonis. Signaling is regulated by a reversible methylation mechanism called adaptation, which also influences the level of basal receptor activation. Mimicking two extreme methylation states in our simulations we found conformational changes for the transmembrane region of NpSRII/NpHtrII which resemble experimentally observed light-induced changes. Further downstream in the cytoplasmic domain of the transducer the signal propagates via distinct changes in the dynamics of HAMP1, HAMP2, the adaptation domain and the binding region for the kinase CheA, where conformational rearrangements were found to be subtle. Overall these observations suggest a signaling mechanism based on dynamic allostery resembling models previously proposed for E. coli chemoreceptors, indicating similar properties of signal transduction for archaeal photoreceptors and bacterial chemoreceptors.Author Summary: Achaea and bacteria can “see” and “sniffle”, they have photo- and chemosensors that measure the environment. On the cell poles, these sensor proteins form large arrays built of several thousands of different receptors. The receptors comprise extracellular or transmembrane sensory domains and elongated homodimeric coiled-coil bundles, which transduce the signals from the membrane across ~20 nm to a conserved cytoplasmic signaling subdomain in an unknown manner. In our study we performed coarse-grained molecular dynamics simulations of the phototactic receptor/transducer complex from Natronomonas pharaonis. Comparing fully methylated and demethylated complexes reveals an interconversion between states of different dynamics along the coiled-coil bundle, which might represent the essential characteristics of the signal transfer from the membrane to the binding sites of the downstream kinase CheA.