Structural and functional comparison of magnesium transporters throughout evolution

Area of Science:

• Biochemistry and Molecular Biology
• Cellular Physiology
• Structural Biology

Background:

• Magnesium (Mg²⁺) is an essential divalent cation vital for numerous cellular processes, including protein synthesis, energy metabolism, and DNA stability.
• Maintaining intracellular Mg²⁺ homeostasis is critical, as disruptions lead to impaired cell growth and metabolic dysfunction.
• Organisms utilize specialized Mg²⁺ channels and transporters to regulate Mg²⁺ influx and efflux, ensuring physiological concentrations.

Purpose of the Study:

• To compare the structure and function of prokaryotic and eukaryotic Mg²⁺ transporters.
• To identify conserved motifs and structural features across different Mg²⁺ transport systems.
• To elucidate how understanding prokaryotic transporters aids in comprehending eukaryotic Mg²⁺ transport mechanisms.

Main Methods:

• Comparative analysis of known prokaryotic Mg²⁺ transporters (CorA, MgtA/B, MgtE, CorB/C).
• Examination of conserved structural motifs, particularly in the selectivity pore.
• Comparison with eukaryotic Mg²⁺ transport systems, including CNNM proteins, TRPM6, and TRPM7.
• Review of functional properties and regulatory integration of eukaryotic channels.

Main Results:

• Conserved selectivity pore motifs were identified in prokaryotic CorA, MgtE, and CorB/C transporters.
• Vertebrate CNNM proteins show potential Mg²⁺ transport capacity as orthologues of CorB/C.
• Eukaryotic TRPM6 and TRPM7 channels possess a unique channel-kinase fusion, integrating regulatory pathways.
• MgtE shares selectivity pore characteristics with eukaryotic SLC41 Na⁺/Mg²⁺ transporters.

Conclusions:

• Structural and functional similarities exist between prokaryotic and eukaryotic Mg²⁺ transporters, particularly in pore regions.
• Prokaryotic Mg²⁺ transporter research provides fundamental insights into conserved mechanisms of magnesium transport.
• Understanding diverse Mg²⁺ transport systems, including channel-kinase fusions, is key to comprehending cellular magnesium homeostasis.