From Bacteria to Man: Archaic Proton-Dependent Peptide Transporters at Work

Abstract

Uptake of nutrients into cells is essential to life and occurs in all organisms at the expense of energy. Whereas in most prokaryotic and simple eukaryotic cells electrochemical transmembrane proton gradients provide the central driving force for nutrient uptake, in higher eukaryotes it is more frequently coupled to sodium movement along the transmembrane sodium gradient, occurs via uniport mechanisms driven by the substrate gradient only, or is linked to the countertransport of a similar organic solute. With the cloning of a large number of mammalian nutrient transport proteins, it became obvious that a few "archaic'' transporters that utilize a transmembrane proton gradient for nutrient transport into cells can still be found in mammals. The present review focuses on the electrogenic peptide transporters as the best studied examples of proton-dependent nutrient transporters in mammals and summarizes the most recent findings on their physiological importance. Taking peptide transport as a general phenomenon found in nature, we also include peptide transport mechanisms in bacteria, yeast, invertebrates, and lower vertebrates, which are not that often addressed in physiology journals.

NRT1.5/NPF7.3 Functions as a Proton-Coupled H+/K+ Antiporter for K+ Loading into the Xylem in Arabidopsis

“…NRT1/PTR is a ubiquitous family that exists in all kingdoms of life (Steiner et al, 1995;Daniel et al, 2006). In contrast to the low number of family members in other organisms, such as in yeast (one), Drosophila melanogaster (three), Caenorhabditis elegans (four), and human (six), the NRT1/PTR family is prevalent in higher plants (Tsay et al, 2007).…”

“…Both families belong to the major facilitator superfamily that represents the largest secondary active transporters in all species (Pao et al, 1998;Law et al, 2008;Yan, 2015). The NRT1/PTR family is also known as the POT (protondependent oligopeptide transporter) family, which is present in all living organisms and prevalent in higher plants, referred to as the NPF (NRT1/PTR family) (Steiner et al, 1995;Daniel et al, 2006;Léran et al, 2014). In Arabidopsis, the NRT1/PTR family contains as many as 53 members, which implies that this family has diverse functions (Tsay et al, 2007).…”

Bacterial peptide transporters: Messengers of nutrition to virulence

“…28 These transporters provide amino acids and nitrogen in all living organisms except archaea. 29 They belong to the major facilitator family (MFS) of transporters as they typically contain 12-18 transmembrane domains which derive their energy of transport from the import of proton. Despite their huge size (600 to 900 amino acids), 30 they are commonly reported to transport small peptides like di-and tripeptides (Table 1).…”

“…37,38 The stoichiometry remains as one proton for cationic or neutral dipeptide, 2 protons for anionic dipeptide and 3 protons for anionic tripeptide, where the extra protons neutralize the charge on the peptide. 29,39,40 Conserved sequences on the transmembrane domains allow specific binding with the peptides and thereby effective transport, like the ExxERFxYY motif on the transmembrane helix 1 (TM1) facilitates hydrogen bond formation with the carboxy terminus of the dipeptide. Similarly, the presence of tyrosine and tryptophan residues on specific transmembrane domains and FWALF motif in TM7 affect the V max and K m of the transport of peptides.…”

Substrates of the human oligopeptide transporter hPEPT2

“…However, the presence of D-amino acids results in the lack of uptake and transport of substrate. Peptides that solely contain D-amino acids do not bind with the substrate-binding domain as free amino acids, and peptides with four or more amino acids do not serve as substrates of PEPT2 (5). Dipeptides that contain proline are poor substrates because of the conformational difference to normal L-α-amino acids (37).…”