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A widened substrate selectivity filter of eukaryotic formate-nitrite transporters enables high-level lactate conductance
- Source :
- The FEBS Journal. 284:2663-2673
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Bacterial formate-nitrite transporters (FNT) regulate the metabolic flow of small weak mono-acids derived from anaerobic mixed-acid fermentation, such as formate, and further transport nitrite, and hydrosulfide. The eukaryotic Plasmodium falciparum FNT is vital for the malaria parasite by its ability to release the larger l-lactate substrate as the metabolic end product of anaerobic glycolysis in symport with protons preventing cytosolic acidification. However, the molecular basis for substrate discrimination by FNTs has remained unclear. Here, we identified a size-selective FNT substrate filter region around an invariant lysine at the bottom of the periplasmic/extracellular vestibule. The selectivity filter is reminiscent of the aromatic/arginine constriction of aquaporin water and solute channels regarding composition, location in the protein, and the size-selection principle. Bioinformatics support an adaptation of the eukaryotic FNT selectivity filter to accommodate larger physiologically relevant substrates. Mutations that affect the diameter at the filter site predictably modulated substrate selectivity. The shape of the vestibule immediately above the filter region further affects selectivity. This study indicates that eukaryotic FNTs evolved to transport larger mono-acid substrates, especially l-lactic acid as a product of energy metabolism. This article is protected by copyright. All rights reserved.
- Subjects :
- 0301 basic medicine
Plasmodium falciparum
Lysine
Aquaporin
Biology
Aquaporins
Biochemistry
Substrate Specificity
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Formate
Lactic Acid
Molecular Biology
Nitrites
Computational Biology
Membrane Transport Proteins
Substrate (chemistry)
Cell Biology
Periplasmic space
Cytosol
030104 developmental biology
chemistry
Anaerobic glycolysis
Mutation
Selectivity
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 1742464X
- Volume :
- 284
- Database :
- OpenAIRE
- Journal :
- The FEBS Journal
- Accession number :
- edsair.doi.dedup.....f13c68a3210f7956ecadba6f881dd0f4