Structural mechanism of TRPV3 channel inhibition by the plant-derived coumarin osthole.

TRPV3, a representative of the vanilloid subfamily of TRP channels, is predominantly expressed in skin keratinocytes and has been implicated in cutaneous sensation and associated with numerous skin pathologies and cancers. TRPV3 is inhibited by the natural coumarin derivative osthole, an active ingredient of Cnidium monnieri, which has been used in traditional Chinese medicine for the treatment of a variety of human diseases. However, the structural basis of channel inhibition by osthole has remained elusive.

Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel.

Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states.

Ion channel reconstitution in lipid bilayers.

Incorporation of ion channels in planar lipid bilayers allows detecting and measuring ion channel activity in a well-controlled system. This technique provides critical information about ion channel kinetics, ion selectivity, gating mechanism, open probability, unitary conductance, subconductance states, voltage dependence, and burst opening events, particularly at the single molecule level. Planar lipid bilayers provide a unique controllable environment that enables maintaining specific regulatory components, including lipids, ligands, inhibitors, particular ions, and proteins, as well as the temperature that can modulate activity of many ion channels.

Inorganic polyphosphate as an energy source in tumorigenesis.

Cancer cells have high demands for energy to maintain their exceedingly proliferative growth. However, the mechanism of energy expenditure in cancer is not well understood. We hypothesize that cancer cells might utilize energy-rich inorganic polyphosphate (polyP), as energetic reserve.

Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice.

Obesity affects over 2 billion people worldwide and is accompanied by peripheral neuropathy (PN) and an associated poorer quality of life. Despite high prevalence, the molecular mechanisms underlying the painful manifestations of PN are poorly understood, and therapies are restricted to use of painkillers or other drugs that do not address the underlying disease. Studies have demonstrated that the gut microbiome is linked to metabolic health and its alteration is associated with many diseases, including obesity.