The Effects of Calcium on Lipid–Protein Interactions and Ion Flux in the Cx26 Connexon Embedded into a POPC Bilayer
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Gap junctions provide a communication pathway between adjacent cells. They are formed by paired connexons that reside in the plasma membrane of their respective cell and their activity can be modulated by the bilayer composition. In this work, we study the dynamic behavior of a Cx26 connexon embedded in a POPC lipid bilayer, studying: the membrane protein interactions and the ion flux though the connexon pore. We analyzed extensive atomistic molecular dynamics simulations for different conditions, 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 presence or absence of the calcium ions and its distribution within the pore.
KeywordsMolecular dynamics Cx26 hemichannel Connexon POPC APBS
The Center for High Performance Computing at The Utah University provided computer resources for High Performance Computing, which was partially funded by the NIH Shared Instrumentation Grant 1S10OD021644-01A1. JCF was partially supported by the University of Utah Center for Clinical and Translational Science under NCATS Grant U01TR002538. MBF was partially supported by the University of Buenos Aires Grant 20020170100456BA and PIP CONICET 11220130100377. MP was partially supported by Grants ANPCyT PICT2014-3653, PIP CONICET0131-2014. Gabriel Ernesto Jara thanks FAPESP and the Center for Computational Engineering and Sciences (CCES) (Grants 2013/08293-7), CNPq (Grant No. 154782/2018-1) for the financial support. MLF was partially supported by Grants UBACYT 20620170100006BA and PIP CONICET 11220170100863CO.
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The authors declare that they have no conflicts of interest.
Research Involving Human and Animal Participants
This article does not contain any data which were gathered by performing live studies on human or animal participants.
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