Magnesium interactions with a CX26 connexon in lipid bilayers

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Connexin 26 (Cx26) hemichannels are crucial for intercellular communication.
• Previous studies identified calcium ion binding sites on Cx26 hemichannels.
• Understanding cation interactions with Cx26 hemichannels is vital for their function.

Purpose of the Study:

• To investigate the interaction of magnesium di-cations with Cx26 hemichannels.
• To compare magnesium binding with previously identified calcium binding sites.
• To elucidate the role of mass and steric effects in cation binding to Cx26.

Main Methods:

• Atomistic molecular dynamics simulations.
• Simulations of Cx26 hemichannel embedded in a POPC bilayer.
• Inclusion of magnesium, sodium, and potassium ions in different solutions.

Main Results:

• Magnesium di-cations showed significantly different binding affinity compared to calcium.
• Magnesium ions strongly bound only to the GLU114 site of one connexin.
• Sodium and potassium ion simulations revealed no specific interactions with the Cx26 hemichannel.

Conclusions:

• Magnesium binding to Cx26 hemichannels is site-specific and less extensive than calcium.
• Mass and steric properties of cations significantly influence their binding to Cx26 hemichannels.
• These findings provide insights into the selectivity of Cx26 hemichannel ion permeation.