The key role of the central cavity in sodium transport through ligand-gated two-pore channels.
Phys Chem Chem Phys
; 23(34): 18461-18474, 2021 Sep 14.
Article
in English
| MEDLINE | ID: covidwho-1373454
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sodium
/
Ion Channel Gating
/
Ligand-Gated Ion Channels
Language:
English
Journal:
Phys Chem Chem Phys
Journal subject:
Biophysics
/
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
D1cp02947a
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