Exploring The Cx26 Hemmichannel using MD simulations

JUAN M.R. ALBANO; GABRIEL JARA; JULIO C. FACELLI; MARTA B. FERRARO; MONIA PICKHOLZ

SAN PABLO

Conferencia; 50 Annual Meeting of SBBq; 2021

SBBq

Gap junctions provide a communication pathway between adjacent cells. They are formed by two connexons that correspond to different cells. In this work, we investigated the dynamic behavior of a Cx26 connexon in a POPC lipid bilayer using Molecular Dynamics simulations. Specific amino acid interactions with cal-cium and their stability were found. Few of these sites such as, GLU42, GLU47, GLY45 and ASP50, were already suggested in the literature. Besides, we identi-fied novel calcium biding sites: ASP2, ASP117, ASP159, GLU114, GLU119, GLU120 and VAL226. Furthermore, we focus our attention on the membrane protein interactions and the ion flux though the connexon pore. We analyzed ex-tensive atomistic simulations with and without calcium ions. We found that lipid-protein interactions were mainly mediated by hydrogen bonds. Specific amino acids were identified forming hydrogen bonds with the POPC lipids (ARG98, ARG127, ARG165, ARG216, LYS22, LYS221, LYS223, LYS224, SER19, SER131, SER162, SER219, SER222, THR18 and TYR97, TYR155, TYR212, and TYR217). In the presence of calcium ions, we found subtle differences on the HB lifetimes. Finally, these MD simulations are able to identify and explain differential chlorine flux through the pore depending on the amount of the calcium ions and its distribution within the pore.