Structural insights into subunit-dependent functional regulation in epithelial sodium channels

Area of Science:

• Molecular biology
• Structural biology
• Biophysics

Background:

• Epithelial sodium channels (ENaCs) are vital for sodium reabsorption in mammals.
• Four subunits (α, β, γ, δ) are known, forming heteromeric complexes, but only the αβγ structure was previously determined.

Purpose of the Study:

• To investigate the formation of ENaC complexes with different subunit compositions.
• To elucidate how individual subunits contribute to distinct channel properties.

Main Methods:

• Co-expression of human δ, β, and γ ENaC subunits.
• Single-particle cryoelectron microscopy (cryo-EM) to determine complex structures.

Main Results:

• Three distinct ENaC complexes were observed.
• The β and γ subunit positions were conserved across complexes.
• The α subunit position could be occupied by either δ or another β subunit.
• The δ subunit induced structural changes in the γ subunit.

Conclusions:

• ENaC subunit composition modulates channel structure and function.
• Observed structural differences between αβγ and δβγ channels offer molecular insights into ENaC activity regulation.