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The key role of the central cavity in sodium transport through ligand-gated two-pore channels #MMPMID34612386
Milenkovic S; Bodrenko IV; Carpaneto A; Ceccarelli M
Phys Chem Chem Phys 2021[Sep]; 23 (34): 18461-18474 PMID34612386show ga
Subcellular and organellar mechanisms have manifested a prominent importance for a broad variety of processes that maintain cellular life at its most basic level. Mammalian two-pore channels (TPCs) appear to be cornerstones of these processes in endo-lysosomes by controlling delicate ion-concentrations in their interiors. With evolutionary remarkable architecture and one-of-a-kind selectivity filter, TPCs are an extremely attractive topic per se. In the light of the current COVID-19 pandemic, hTPC2 emerges to be more than attractive. As a key regulator of the endocytosis pathway, it is potentially essential for diverse viral infections in humans, as demonstrated. Here, by means of multiscale molecular simulations, we propose a model of sodium transport from the lumen to the cytosol where the central cavity works as a reservoir. Since the inhibition of hTPC2 is proven to stop SARS-CoV2 in vitro, shedding light on the hTPC2 function and mechanism is the first step towards the selection of potential inhibiting candidates.
|*Ion Channel Gating[MESH]
|COVID-19[MESH]
|Ligand-Gated Ion Channels/metabolism/*physiology[MESH]
Phys+Chem+Chem+Phys 2021 ; 23 (34): 18461-18474
