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Magnesium interactions with a CX26 connexon in lipid bilayers

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Abstract

Following our previous work, where we described the interaction of calcium with the Cx26 hemichannel, we further explore the same system by atomistic molecular dynamics simulations considering a different di-cation, magnesium. Specifically, the interaction of magnesium di-cation with the previously reported calcium binding sites (ASP2, ASP117, ASP159, GLU114, GLU119, GLU120, and VAL226) was investigated to identify similarities and differences between them. In order to do so, four extensive simulations were carried out. Two of them considered a Cx26 hemichannel embedded on a POPC bilayer with one of the di-cations and a sodium-chlorine solution. For the remaining two, no di-cations were included and a sodium-chlorine or potassium-chlorine solution was considered. Potassium has a similar atomic mass to calcium, and sodium to magnesium, but they both differ in charge (1e and 2e respectively). Magnesium and calcium, even having the same charge, showed different affinity for the explored protein. From the calcium binding sites referred above, we found that the magnesium di-cations only binds strongly to the GLU114 site of one connexin. For the sodium and potassium simulations, no specific interactions with the protein were found. Altogether, these results suggest that mass and steric effects play an important role in determining cation binding to Cx26 hemichannels.

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Funding

The Center for High Performance Computing at The Utah University provided computer resources for High Performance Computing, which has been partially funded by the NIH Shared Instrumentation Grant 1S10OD021644-01A1. JCF has been partially supported by the University of Utah Center for Clinical and Translational Science under NCATS Grant U01TR002538. MBF has been partially supported by the University of Buenos Aires Grant 20020170100456BA and PIP CONICET 11220130100377. JMRA has been partially supported by the Florencio Fiorini Foundation. MP has been partially supported by grants ANPCyT PICT2014- 3653, PIP CONICET0131-2014.

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Authors and Affiliations

  1. Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IFIBA, CONICET, Ciudad Universitaria, Pabellón 1, 1428, Buenos Aires, Argentina

    Juan M. R. Albano, Marta B. Ferraro & Monica Pickholz

  2. Instituto de Física de Buenos Aires (IFIBA), CONICET–Universidad de Buenos Aires, Buenos Aires, Argentina

    Juan M. R. Albano, Marta B. Ferraro & Monica Pickholz

  3. Department of Biomedical Informatics, University of Utah, 421 Wakara Way, Suite 140, Salt Lake City, UT, 84108, USA

    Julio C. Facelli

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  1. Juan M. R. Albano
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Correspondence to Marta B. Ferraro.

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This paper belongs to Topical Collection QUITEL 2018 (44th Congress of Theoretical Chemists of Latin Expression)

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Albano, J.M.R., Facelli, J.C., Ferraro, M.B. et al. Magnesium interactions with a CX26 connexon in lipid bilayers. J Mol Model 25, 232 (2019). https://doi.org/10.1007/s00894-019-4121-5

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