Aquaglyceroporin 2 (from Trypanosoma brucei) (TbAQP2)

Aquaglyceroporin 2 in *Trypanosoma brucei* (TbAQP2) is an integral membrane protein of the major intrinsic protein (MIP) family that forms homotetramers in the plasma membrane, with each monomer facilitating the passage of water, glycerol, and other small molecules. Unlike canonical aquaglyceroporins, TbAQP2 has a unique selectivity filter lacking the typical NPA and ar/R motifs, enabling it to conduct not only endogenous solutes but also the anti-trypanosomal drugs pentamidine and melarsoprol. Structural adaptations allow the channel pore to accommodate bulky drug molecules, making TbAQP2 critical for drug uptake and hence for the efficacy of therapy in African sleeping sickness. Mutations or deletions in the TbAQP2 gene are closely associated with resistance to these drugs, underlining its importance as both a therapeutic target and a biomarker for drug resistance.

Other names

AQP2 (note: in T. brucei context; do not confuse with mammalian AQP2)Aquaporin 2, Trypanosoma brucei aquaglyceroporin 2

Uptake of pentamidine and melarsoprol by direct permeation through the TbAQP2 channel in T. brucei plasma membrane. Drug-resistant parasites often have altered or missing TbAQP2, blocking drug uptake.