Molecular dissection of water and glycerol permeability of the aquaglyceroporin from Plasmodium falciparum by mutational analysis

Eric Beitz, Slavica Pavlovic-Djuranovic, Masato Yasui, Peter Agre, Joachim E. Schultz

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Abstract

The selectivity of aquaporins for water and solutes is determined by pore diameter. Paradoxically, the wider pores of glycerol facilitators restrict water passage by an unknown mechanism. Earlier we characterized an aquaglyceroporin from Plasmodium falciparum with high permeability for both glycerol and water. We use point mutations to demonstrate that amino acids directly lining the pore are not responsible for the excellent water permeability of the Plasmodium aquaglyceroporin but affect permeability of pentitols. Within a conserved WET triad in the extracellular C-loop we identified a Plasmodium aquaglyceroporin-specific glutamate (E125) located in proximity to a conserved arginine (R196) at the pore mouth. Mutation of E125 to serine largely abolished water permeability. Concomitantly, the activation energy for water permeation was increased by 4 kcal/mol. Mutation of the adjacent tryptophan to cysteine led to irreversible inhibition of water passage by Hg2+. This unequivocally proves the proximity of the couple WI24/E125 close to the pore mouth. We conclude that in the Plasmodium aquaglyceroporin the electrostatic environment at the extracellular pore entry regulates water permeability.

Original languageEnglish
Pages (from-to)1153-1158
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number5
DOIs
Publication statusPublished - 2004 Feb 3
Externally publishedYes

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Aquaglyceroporins
Plasmodium falciparum
Glycerol
Dissection
Permeability
Water
Plasmodium
Mouth
Aquaporins
Mutation
Static Electricity
Point Mutation
Tryptophan
Serine
Cysteine
Arginine
Glutamic Acid

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Molecular dissection of water and glycerol permeability of the aquaglyceroporin from Plasmodium falciparum by mutational analysis. / Beitz, Eric; Pavlovic-Djuranovic, Slavica; Yasui, Masato; Agre, Peter; Schultz, Joachim E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 5, 03.02.2004, p. 1153-1158.

Research output: Contribution to journalArticle

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