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Aquaporins with anion/monocarboxylate permeability: mechanisms, relevance for pathogen-host interactions.

Rambow J, Wu B, Rönfeldt D, Beitz E - Front Pharmacol (2014)

Bottom Line: It became apparent that not all aquaporins clearly fit into one of only two subfamilies.Here, we summarize the findings on aquaporin anion transport, analyze the pore layout of such aquaporins in comparison to prototypical non-selective anion channels, monocarboxylate transporters, and formate-nitrite transporters.Finally, we discuss in which scenarios anion conducting aquaporins may be of physiological relevance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrechts-University of Kiel Kiel, Germany.

ABSTRACT
Classically, aquaporins are divided based on pore selectivity into water specific, orthodox aquaporins and solute-facilitating aquaglyceroporins, which conduct, e.g., glycerol and urea. However, more aquaporin-passing substrates have been identified over the years, such as the gasses ammonia and carbon dioxide or the water-related hydrogen peroxide. It became apparent that not all aquaporins clearly fit into one of only two subfamilies. Furthermore, certain aquaporins from both major subfamilies have been reported to conduct inorganic anions, such as chloride, or monoacids/monocarboxylates, such as lactic acid/lactate. Here, we summarize the findings on aquaporin anion transport, analyze the pore layout of such aquaporins in comparison to prototypical non-selective anion channels, monocarboxylate transporters, and formate-nitrite transporters. Finally, we discuss in which scenarios anion conducting aquaporins may be of physiological relevance.

No MeSH data available.


Related in: MedlinePlus

Protein structure of an AQP monomer. (A) Slab of AQP1 showing the channel and the two constriction sites. The positive electrostatic field emanating from the channel is symbolized by the blue transparent shading. (B) Typical amino acid composition of the ar/R region in a water specific AQP (here AQP1; PDB #1J4N; Borgnia et al., 1999) and an aquaglyceroporin (here Escherichia coli GlpF; PDB #1FX8; Fu et al., 2000). (C) Half helices B and E with the capping asparagine residues residing at the positive helix ends.
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Figure 1: Protein structure of an AQP monomer. (A) Slab of AQP1 showing the channel and the two constriction sites. The positive electrostatic field emanating from the channel is symbolized by the blue transparent shading. (B) Typical amino acid composition of the ar/R region in a water specific AQP (here AQP1; PDB #1J4N; Borgnia et al., 1999) and an aquaglyceroporin (here Escherichia coli GlpF; PDB #1FX8; Fu et al., 2000). (C) Half helices B and E with the capping asparagine residues residing at the positive helix ends.

Mentions: Cellular aquaporin water channels (AQPs) constitute a large family of transmembrane proteins throughout all kingdoms of life (Abascal et al., 2014). AQPs are members of the major intrinsic protein (MIP) family and feature a uniform molecular structure consisting of six transmembrane spans and two half helices that form a seventh pseudo-transmembrane domain (Murata et al., 2000). AQPs are arranged as homotetramers with each monomer contributing an individual transduction channel. The central pore of certain AQP tetramers appears to enable permeation of gaseous substrates (Geyer et al., 2013). Since their discovery about 20 years ago it has become apparent that AQPs conduct a variety of substrates besides water (Wu and Beitz, 2007). Among these are small, uncharged polyols, such as glycerol, other solutes, such as carbonyl compounds (Pavlovic-Djuranovic et al., 2006), urea, or hydrogen peroxide (Bienert et al., 2007; Almasalmeh et al., 2014). Even neutral, protonated arsenous (Liu et al., 2002; Wu et al., 2010) and silicic acid (Ma et al., 2006) have been found to pass. Further substrates of AQPs are solubilized gasses, namely ammonia (Jahn et al., 2004; Zeuthen et al., 2006) and carbon dioxide (Nakhoul et al., 1998). Especially the latter has been linked to permeation through the central pore (Musa-Aziz et al., 2009). Apart from this, AQPs are rather strict about the exclusion of charged substrates. None of the known natural AQPs was found to conduct cations, such as protons (Murata et al., 2000; Tajkhorshid et al., 2002; Ilan et al., 2004; de Groot and Grubmüller, 2005; Beitz et al., 2006b; Li et al., 2011; Wree et al., 2011), inorganic cations (Na+, K+; Wu et al., 2009), or ammonium (NH4+; Beitz et al., 2006b; Zeuthen et al., 2006). The case appears somewhat less stringent when it comes to anion permeability of AQPs as discussed in this review. Generally, AQPs have two selective motives. One is located at the extracellular mouth of the pore displaying a highly conserved arginine residue in an aromatic surrounding, the so-called selectivity filter or aromatic arginine (ar/R) region. A second one resides in the center of the channel where the two half helices meet (Figure 1; de Groot and Grubmüller, 2001). This second constriction comprises two well-conserved Asn-Pro-Ala triplets (NPA) as capping structures of the half helices with the two Asn residues pointing toward the channel lumen. The diameter of the ar/R region defines selectivity by size exclusion resulting in water specific, orthodox AQPs (<2.8 Å) or glycerol/urea-conducting aquaglyceroporins (>3.4 Å; Fu et al., 2000; Tajkhorshid et al., 2002; de Groot and Grubmüller, 2005; Beitz et al., 2006b). Due to its positive charge, the ar/R region is further involved in proton repulsion (Beitz et al., 2006b; Li et al., 2011). It further forms a joint filter together with the electrostatic field emanating from the positive ends of the half-helix dipoles in the NPA region against the passage of inorganic cations (Wu et al., 2009; Wree et al., 2011; Kosinska Eriksson et al., 2013).


Aquaporins with anion/monocarboxylate permeability: mechanisms, relevance for pathogen-host interactions.

Rambow J, Wu B, Rönfeldt D, Beitz E - Front Pharmacol (2014)

Protein structure of an AQP monomer. (A) Slab of AQP1 showing the channel and the two constriction sites. The positive electrostatic field emanating from the channel is symbolized by the blue transparent shading. (B) Typical amino acid composition of the ar/R region in a water specific AQP (here AQP1; PDB #1J4N; Borgnia et al., 1999) and an aquaglyceroporin (here Escherichia coli GlpF; PDB #1FX8; Fu et al., 2000). (C) Half helices B and E with the capping asparagine residues residing at the positive helix ends.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150397&req=5

Figure 1: Protein structure of an AQP monomer. (A) Slab of AQP1 showing the channel and the two constriction sites. The positive electrostatic field emanating from the channel is symbolized by the blue transparent shading. (B) Typical amino acid composition of the ar/R region in a water specific AQP (here AQP1; PDB #1J4N; Borgnia et al., 1999) and an aquaglyceroporin (here Escherichia coli GlpF; PDB #1FX8; Fu et al., 2000). (C) Half helices B and E with the capping asparagine residues residing at the positive helix ends.
Mentions: Cellular aquaporin water channels (AQPs) constitute a large family of transmembrane proteins throughout all kingdoms of life (Abascal et al., 2014). AQPs are members of the major intrinsic protein (MIP) family and feature a uniform molecular structure consisting of six transmembrane spans and two half helices that form a seventh pseudo-transmembrane domain (Murata et al., 2000). AQPs are arranged as homotetramers with each monomer contributing an individual transduction channel. The central pore of certain AQP tetramers appears to enable permeation of gaseous substrates (Geyer et al., 2013). Since their discovery about 20 years ago it has become apparent that AQPs conduct a variety of substrates besides water (Wu and Beitz, 2007). Among these are small, uncharged polyols, such as glycerol, other solutes, such as carbonyl compounds (Pavlovic-Djuranovic et al., 2006), urea, or hydrogen peroxide (Bienert et al., 2007; Almasalmeh et al., 2014). Even neutral, protonated arsenous (Liu et al., 2002; Wu et al., 2010) and silicic acid (Ma et al., 2006) have been found to pass. Further substrates of AQPs are solubilized gasses, namely ammonia (Jahn et al., 2004; Zeuthen et al., 2006) and carbon dioxide (Nakhoul et al., 1998). Especially the latter has been linked to permeation through the central pore (Musa-Aziz et al., 2009). Apart from this, AQPs are rather strict about the exclusion of charged substrates. None of the known natural AQPs was found to conduct cations, such as protons (Murata et al., 2000; Tajkhorshid et al., 2002; Ilan et al., 2004; de Groot and Grubmüller, 2005; Beitz et al., 2006b; Li et al., 2011; Wree et al., 2011), inorganic cations (Na+, K+; Wu et al., 2009), or ammonium (NH4+; Beitz et al., 2006b; Zeuthen et al., 2006). The case appears somewhat less stringent when it comes to anion permeability of AQPs as discussed in this review. Generally, AQPs have two selective motives. One is located at the extracellular mouth of the pore displaying a highly conserved arginine residue in an aromatic surrounding, the so-called selectivity filter or aromatic arginine (ar/R) region. A second one resides in the center of the channel where the two half helices meet (Figure 1; de Groot and Grubmüller, 2001). This second constriction comprises two well-conserved Asn-Pro-Ala triplets (NPA) as capping structures of the half helices with the two Asn residues pointing toward the channel lumen. The diameter of the ar/R region defines selectivity by size exclusion resulting in water specific, orthodox AQPs (<2.8 Å) or glycerol/urea-conducting aquaglyceroporins (>3.4 Å; Fu et al., 2000; Tajkhorshid et al., 2002; de Groot and Grubmüller, 2005; Beitz et al., 2006b). Due to its positive charge, the ar/R region is further involved in proton repulsion (Beitz et al., 2006b; Li et al., 2011). It further forms a joint filter together with the electrostatic field emanating from the positive ends of the half-helix dipoles in the NPA region against the passage of inorganic cations (Wu et al., 2009; Wree et al., 2011; Kosinska Eriksson et al., 2013).

Bottom Line: It became apparent that not all aquaporins clearly fit into one of only two subfamilies.Here, we summarize the findings on aquaporin anion transport, analyze the pore layout of such aquaporins in comparison to prototypical non-selective anion channels, monocarboxylate transporters, and formate-nitrite transporters.Finally, we discuss in which scenarios anion conducting aquaporins may be of physiological relevance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrechts-University of Kiel Kiel, Germany.

ABSTRACT
Classically, aquaporins are divided based on pore selectivity into water specific, orthodox aquaporins and solute-facilitating aquaglyceroporins, which conduct, e.g., glycerol and urea. However, more aquaporin-passing substrates have been identified over the years, such as the gasses ammonia and carbon dioxide or the water-related hydrogen peroxide. It became apparent that not all aquaporins clearly fit into one of only two subfamilies. Furthermore, certain aquaporins from both major subfamilies have been reported to conduct inorganic anions, such as chloride, or monoacids/monocarboxylates, such as lactic acid/lactate. Here, we summarize the findings on aquaporin anion transport, analyze the pore layout of such aquaporins in comparison to prototypical non-selective anion channels, monocarboxylate transporters, and formate-nitrite transporters. Finally, we discuss in which scenarios anion conducting aquaporins may be of physiological relevance.

No MeSH data available.


Related in: MedlinePlus