The impact of pathogenic and artificial mutations on Claudin-5 selectivity from molecular dynamics simulations.

ABSTRACT: Tight-junctions (TJs) are multi-protein complexes between adjacent endothelial or epithelial cells. In the blood-brain-barrier (BBB), they seal the paracellular space and the Claudin-5 (Cldn5) protein forms their backbone. Despite the fundamental role in brain homeostasis, little is known on Cldn5-based TJ assemblies. Different structural models were suggested, with Cldn5 protomers generating paracellular pores that restrict the passage of ions and small molecules. Recently, the first Cldn5 pathogenic mutation, G60R, was identified and shown to induce Cl^--selective channels and Na⁺ barriers in BBB TJs, providing an excellent opportunity to validate the structural models. Here, we used molecular dynamics to study the permeation of ions and water through two distinct G6

SUBMITTER: Berselli A 

PROVIDER: S-EPMC10149405 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature