1.H.1.1.9
Claudin 15 (with a cation selective paracellular channel (Angelow et al., 2008).  Claudin-15 is highly expressed in the intestine where it forms efficient Na⁺ channels and Cl^- barriers. The permeation process of Na⁺, K⁺, and Cl^- ions inside a refined structural model of a claudin-15 paracellular channel was investigated using all-atom molecular dynamics simulations in a double-bilayer (Alberini et al. 2018). The channel allows the passage of the two physiological cations while excluding chloride with 30x selectivity. These features are generated by the action of several acidic residues, in particular, the ring of D55 residues which is located at the narrowest region of the pore, in correspondence with the energy minimum for cations and the peak for chloride. Claudin-15 thus regulates tight junction selectivity by invoking the experimentally determined role of the acidic residues (Alberini et al. 2018). Water and small cations can pass through the channel, but larger cations, such as tetramethylammonium, do not (Samanta et al. 2018). TMS 3 plays a role in claudin-15 strand flexibility (Fuladi et al. 2022). Specifically, the kink in TMS 3 skews the rotational flexibility of claudin-15 in the strands and limits their fluctuation (Fuladi et al. 2022).