The AQP2 mutation V71M causesnephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog

Abstract

Several point mutations have been identified in human aquaporins, but their effects on the function of the respective aquaporins are mostly enigmatic. We analyzed the impact of the aquaporin 2 mutation V71M, which causesnephrogenic diabetes insipidus in humans, on aquaporin structure and activity, using the bacterial aquaglyceroporin GlpF as a model. Importantly, the sequence and structure around the V71M mutation is highly conserved between aquaporin 2 and GlpF. The V71M mutation neither impairs substrate flux nor oligomerization of the aquaglyceroporin. Therefore, the human aquaporin 2 mutant V71M is most likely active, but cellular trafficking is probably impaired.

Keywords

• GlpF
• Aquaporin
• Nephrogenic diabetes insipidus
• Activity
• Protein oligomerization