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In this work, we studied the interaction of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    with C\u2010hCx46 and C\u2010hCx26 using molecular dynamics simulations. Unlike other connexons such as the connexon formed by human connexin 26 (C\u2010hCx26), where Ca\n                    <jats:sup>2+<\/jats:sup>\n                    binds to specific sites, in C\u2010hCx46 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    interacts with a toroidal confinement zone limited by negatively charged residues, whose symmetrical distribution allows it to move freely without varying its total attraction potential. This symmetry is lost in C\u2010hCx26 due to the substitution of one of these residues by a lysine, which causes Ca\n                    <jats:sup>2+<\/jats:sup>\n                    to be trapped in specific regions where the electrostatic attraction force is greater. In C\u2010hCx46 a negative electrostatic potential is observed inside the pore, which is screened when interacting with Ca\n                    <jats:sup>2+<\/jats:sup>\n                    . In addition, the presence of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    reduces potassium and water permeability.\n                  <\/jats:p>","DOI":"10.1002\/pro.70691","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:57:13Z","timestamp":1783594633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A symmetric region produces a novel calcium binding mode in the human Cx46 connexon"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5790-3059","authenticated-orcid":false,"given":"Cristopher","family":"Stepke","sequence":"first","affiliation":[{"name":"Centro Interdisciplinario de Neurociencias de Valpara\u00edso (CINV)  Valparaiso Chile"},{"name":"Facultad de Ciencias Universidad de Valparaiso  Valparaiso 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