Inner and Outer Coordination Shells of Mg(2+) in CorA Selectivity Filter from Molecular Dynamics Simulations

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• CorA Mg(2+) channels are crucial for magnesium ion transport.
• The Gly-Met-Asn (GMN) motif in CorA forms the selectivity filter.
• Limited understanding of Mg(2+) cation selectivity in these channels.

Purpose of the Study:

• Investigate Mg(2+) hydration structure and ligand coordination within the CorA selectivity filter.
• Elucidate the role of the GMN motif in Mg(2+) binding and selectivity.
• Compare Mg(2+) coordination in the filter versus bulk water.

Main Methods:

• Molecular dynamics (MD) simulations were employed.
• Analyzed Mg(2+) hydration shells and interactions with filter residues.
• Examined the impact of Mg(2+) removal on filter structure.

Main Results:

• Mg(2+) inner-shell structure in the filter resembles bulk water.
• Outer-shell water structure differs significantly, with GMN residues acting as indirect ligands.
• GMN motif interactions compensate for lost hydrogen bonds, stabilizing Mg(2+) binding.
• Some second-shell waters remain in the filter, reducing mobility and supporting metal binding.

Conclusions:

• The GMN motif enhances Mg(2+) binding affinity in the CorA selectivity filter by serving as an outer coordination ligand.
• This interaction is critical for the channel's function in magnesium homeostasis.
• MD simulations provide valuable insights into ion channel selectivity mechanisms.