Directionality Reversal and Shift of Rotational Axis in a Hemithioindigo Macrocyclic Molecular Motor.

Molecular motors are central driving units for nanomachinery, and control of their directional motions is of fundamental importance for their functions. Light-driven variants use easy to provide, easy to dose, and waste-free fuel with high energy content, making them particularly interesting for applications. Typically, light-driven molecular motors work via rotations around dedicated chemical bonds where the directionality of the rotation is dictated by the steric effects of asymmetry in close vicinity to the rotation axis.

Rhodanine-Based Chromophores: Fast Access to Capable Photoswitches and Application in Light-Induced Apoptosis.

Molecular photoswitches are highly desirable in all chemistry-related areas of research. They provide effective outside control over geometric and electronic changes at the nanoscale using an easy to apply, waste-free stimulus. However, simple and effective access to such molecular tools is typically not granted, and elaborate syntheses and substitution schemes are needed in order to obtain efficient photoswitching properties.

A High-Throughput Fluorescence Polarization-Based Assay for the SH2 Domain of STAT4.

The signal transducer and activation of transcription (STAT) proteins are a family of Src homology 2 (SH2) domain-containing transcription factors. The family member STAT4 is a mediator of IL-12 signalling and has been implicated in the pathogenesis of multiple autoimmune diseases. The activity of STAT4 requires binding of phosphotyrosine-containing motifs to its SH2 domain.

Steric Effects on the Thermal Processes of Hemithioindigo Based Molecular Motor Rotation.

Tuning the thermal behavior of light driven molecular motors is fundamentally important for their future rational design. In many molecular motors thermal ratcheting steps are comprised of helicity inversions, energetically stabilizing the initial photoproducts. In this work we investigated a series of five hemithioindigo (HTI) based molecular motors to reveal the influence of steric hindrance in close proximity to the rotation axle on this process.

Gene editing and synthetically accessible inhibitors reveal role for TPC2 in HCC cell proliferation and tumor growth.

The role of two-pore channel 2 (TPC2), one of the few cation channels localized on endolysosomal membranes, in cancer remains poorly understood. Here, we report that TPC2 knockout reduces proliferation of cancer cells in vitro, affects their energy metabolism, and successfully abrogates tumor growth in vivo. Concurrently, we have developed simplified analogs of the alkaloid tetrandrine as potent TPC2 inhibitors by screening a library of synthesized benzyltetrahydroisoquinoline derivatives.

Author Correction: Identifying ionic interactions within a membrane using BLaTM, a genetic tool to measure homo- and heterotypic transmembrane helix-helix interactions.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Reversible Photoswitching of Isolated Ionic Hemiindigos with Visible Light.

Indigoid chromophores have emerged as versatile molecular photoswitches, offering efficient reversible photoisomerization upon exposure to visible light. Here we report synthesis of a new class of permanently charged hemiindigos (HIs) and characterization of photochemical properties in gas phase and solution. Gas-phase studies, which involve exposing mobility-selected ions in a tandem ion mobility mass spectrometer to tunable wavelength laser radiation, demonstrate that the isolated HI ions are photochromic and can be reversibly photoswitched between Z and E isomers.

A conserved RNA seed-pairing domain directs small RNA-mediated stress resistance in enterobacteria.

Small regulatory RNAs (sRNAs) are crucial components of many stress response systems. The envelope stress response (ESR) of Gram-negative bacteria is a paradigm for sRNA-mediated stress management and involves, among other factors, the alternative sigma factor E (σ ) and one or more sRNAs. In this study, we identified the MicV sRNA as a new member of the σ regulon in Vibrio cholerae.

Conformationally Flexible Sites within the Transmembrane Helices of Amyloid Precursor Protein and Notch1 Receptor.

Intramembrane proteases typically cleave multiple substrates within their transmembrane domains (TMDs). Because substrate TMDs lack a consensus sequence around their scissile sites, it remains unclear how the enzyme discriminates substrates from nonsubstrates at the level of their TMDs. Here, we compare the previously well investigated TMDs of γ-secretase substrates C99 and Notch1 in terms of helix flexibility.

Plastoglobular protein 18 is involved in chloroplast function and thylakoid formation.

Plastoglobules are lipoprotein particles that are found in different types of plastids. They contain a very specific and specialized set of lipids and proteins. Plastoglobules are highly dynamic in size and shape, and are therefore thought to participate in adaptation processes during either abiotic or biotic stresses or transitions between developmental stages.

Phenotypic Heterogeneity Generated by Histidine Kinase-Based Signaling Networks.

A complex relationship exists between environmental factors, signaling networks and phenotypic individuality in bacteria. In this review, we will focus on the organization, function and control points of multiple-input histidine kinase-based signaling cascades as a source of phenotypic heterogeneity. In particular, we will examine the quorum sensing cascade in Vibrio harveyi and the pyruvate sensor network in Escherichia coli.

A brief history of thylakoid biogenesis.

The thylakoid membrane network inside chloroplasts harbours the protein complexes that are necessary for the light-dependent reactions of photosynthesis. Cellular processes for building and altering this membrane network are therefore essential for life on Earth. Nevertheless, detailed molecular processes concerning the origin and synthesis of the thylakoids remain elusive.

mRNA dynamics and alternative conformations adopted under low and high arginine concentrations control polyamine biosynthesis in Salmonella.

Putrescine belongs to the large group of polyamines, an essential class of metabolites that exists throughout all kingdoms of life. The Salmonella speF gene encodes an inducible ornithine decarboxylase that produces putrescine from ornithine. Putrescine can be also synthesized from arginine in a parallel metabolic pathway.

Three autoinducer molecules act in concert to control virulence gene expression in Vibrio cholerae.

Bacteria use quorum sensing to monitor cell density and coordinate group behaviours. In Vibrio cholerae, the causative agent of the diarrheal disease cholera, quorum sensing is connected to virulence gene expression via the two autoinducer molecules, AI-2 and CAI-1. Both autoinducers share one signal transduction pathway to control the production of AphA, a key transcriptional activator of biofilm formation and virulence genes.

The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis.

Zebrafish have a high capacity to replace lost neurons after brain injury. New neurons involved in repair are generated by a specific set of glial cells, known as ependymoglial cells. We analyze changes in the transcriptome of ependymoglial cells and their progeny after injury to infer the molecular pathways governing restorative neurogenesis.

Transcriptomic Approaches for Studying Quorum Sensing in Vibrio cholerae.

Transcriptome analysis using RNA-sequencing (RNA-seq) has now become the standard approach to determine the transcriptional output of an organism. Various modifications to this technology have been developed over the years, usually aiming to improve the annotation of transcript borders, or to identify novel classes of RNAs, such as small regulatory RNAs (sRNAs) and antisense transcripts. RNA-seq has also led to the identification of dozens of new sRNAs in the major human pathogen, Vibrio cholerae.

Photon-Only Molecular Motor with Reverse Temperature-Dependent Efficiency.

Light-driven molecular motors are archetypal molecular machines and enable fast and efficient unidirectional motions under photoirradiation. Their common working mechanism contains thermal ratcheting steps leading to slowed-down and even halted directional movement at lower temperatures. In this work, an alternative type of molecular motor is presented, which operates without thermal ratcheting in the ground state.

A hemithioindigo molecular motor for metal surface attachment.

Functionalization of surfaces with responsive molecular entities is currently an important research field allowing the organization of molecular functions in space in a defined way and thus accessing emergent properties not observed in solution. Herein we report on the synthesis of a hemithioindigo molecular motor bearing thioether feet for surface attachment on its thioindigo fragment. We also give a full theoretical description of its ground state energy profile together with an experimental evaluation of the visible light driven unidirectional rotation in solution.

Circular Dichroism Photoswitching with a Twist: Axially Chiral Hemiindigo.

Chiroptical properties play a crucial role not only for molecular structures and their functions but also for advanced applications such as molecular sensing, absolute asymmetric synthesis, or information processing and storage. Manipulating chiroptical characteristics in a predictable and reversible fashion by outside means is therefore a highly desirable option to enhance the functions and reporting abilities of a molecular system. Herein, we present axially chiral hemiindigo photoswitches showing unusual chiroptical changes upon visible-light irradiation.

Cross-Regulation between Bacteria and Phages at a Posttranscriptional Level.

The study of bacteriophages (phages) and prophages has provided key insights into almost every cellular process as well as led to the discovery of unexpected new mechanisms and the development of valuable tools. This is exemplified for RNA-based regulation. For instance, the characterization and exploitation of the antiphage CRISPR (clustered regularly interspaced short palindromic repeat) systems is revolutionizing molecular biology.

Optimization of sample preparation and green color imaging using the mNeonGreen fluorescent protein in bacterial cells for photoactivated localization microscopy.

mNeonGreen fluorescent protein is capable of photo-switching, hence in principle applicable for super-resolution imaging. However, difficult-to-control blinking kinetics that lead to simultaneous emission of multiple nearby mNeonGreen molecules impedes its use for PALM. Here, we determined the on- and off- switching rate and the influence of illumination power on the simultaneous emission.

Direct evidence for hula twist and single-bond rotation photoproducts.

Photoisomerization reactions are quintessential processes driving molecular machines and motors, govern smart materials, catalytic processes, and photopharmacology, and lie at the heart of vision, phototaxis, or vitamin production. Despite this plethora of applications fundamental photoisomerization mechanisms are not well understood at present. The famous hula-twist motion-a coupled single and double-bond rotation-was proposed to explain proficient photoswitching in restricted environments but fast thermal follow-up reactions hamper identification of primary photo products.

FZL is primarily localized to the inner chloroplast membrane however influences thylakoid maintenance.

FZL is primarily localized to the chloroplast inner envelope and not to the thylakoids, but nevertheless affects the maintenance of thylakoid membranes and photosynthetic protein complexes. The fuzzy-onion-like protein (FZL) is a membrane-bound dynamin-like GTPase located in the chloroplast. We have investigated the chloroplast sub-localization of the endogenous FZL protein and found it to be primarily localized to the inner envelope.

Transmembrane Helix Induces Membrane Fusion through Lipid Binding and Splay.

The fusion of biological membranes may require splayed lipids whose tails transiently visit the headgroup region of the bilayer, a scenario suggested by molecular dynamics simulations. Here, we examined the lipid splay hypothesis experimentally by relating liposome fusion and lipid splay induced by model transmembrane domains (TMDs). Our results reveal that a conformationally flexible transmembrane helix promotes outer leaflet mixing and lipid splay more strongly than a conformationally rigid one.