Cation selectivity by the CorA Mg2+ channel requires a fully hydrated cation

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• The CorA channel is crucial for magnesium ion (Mg2+) uptake in many bacteria and archaea.
• The mechanism of Mg2+ selectivity in CorA remains poorly understood.
• Previous studies suggested CorA binds hydrated Mg2+ ions, differing from other ion channels.

Purpose of the Study:

• To investigate the role of the conserved periplasmic loop in the Mg2+ selectivity of the CorA channel.
• To elucidate the structural and functional basis of Mg2+ binding and transport through CorA.

Main Methods:

• Crystallography to determine the structure of Thermotoga maritima CorA.
• Site-directed mutagenesis of conserved residues in the periplasmic loop.
• In vitro transport assays to evaluate channel function of mutants.

Main Results:

• Mutations in charged residues (E281, K287) of the periplasmic loop had minimal impact on function.
• Mutations at E285, while affecting function, indicated the negative charge is not essential for selectivity.
• Mutations at K287 and W288 disrupted cooperative Mg2+ binding sites, suggesting a role beyond simple electrostatic interaction.
• Results are inconsistent with direct electrostatic interaction of Mg2+ with the loop.

Conclusions:

• The CorA periplasmic loop acts as an initial binding site for hydrated Mg2+ ions.
• The loop likely facilitates the dehydration of Mg2+ prior to its entry into the channel pore.
• This mechanism explains Mg2+ selectivity without direct electrostatic interactions within the loop.