Molecular and Structural Features of the Proton-Coupled Oligopeptide Transporter Superfamily
Section snippets
Two Different Peptide Transporter Subfamilies: A Comparison between the Members of the ABC Peptide Transporter Subfamily and the POT Subfamily
The ABC (for ATP-binding cassette) transporter superfamily is ubiquitous, present in both prokaryotic and eukaryotic kingdoms, and is involved in many important biological processes, such as transport of nutrients (e.g., amino acids, sugars, and oligopeptides) and ions (e.g., Cl‒, K+), secretion of metabolic waste products, antigen presentation and development of multiple drug resistance in cancer cells 25., 26.. The members of the ABC transporter superfamily are operated by directly “burning”
Molecular Cloning Procedures Employed for Identification of the POT Family Members
cDNA cloning of functional cellular proteins remains one of the most arduous challenges in the contemporary molecular biology field, especially when the transcripts from the genes are present in low abundance. In recent years, several investigators have used different molecular biological techniques to clone more than a dozen members of the proton-dependent oligopeptide transporter (POT) family. Here we adapt the nomenclature of Paulsen and Skurray (27), who initially coined the term “POT” for
Comparison of Amino Acid Sequences of the Members of the POT Family
General structural features of individual members of the POT subfamily, the size and distinct structural profile of the transporter genes or cDNAs, predicted amino acid composition, molecular mass of the protein core, isoelectric point (pI), consensus glycosylation sites, and the potential phosphorylation sites (Ser or Thr) for protein kinase C and protein kinase A (for the mammalian POT members only) of the transporter proteins are listed in Table I. The gene symbols and generic names are kept
Topological Features of the POT Subfamily
The POT subfamily members are present in prokaryotic as well as in eukaryotic cells and share certain common structural and functional characteristics. It is believed that all of the carrier-mediated transport systems, including facilitative transporters, antiporters, and ion-coupled symporters, operate by similar mechanisms. This solute transport family, called the major facilitator superfamily (MFS), has an ancient evolutionary history and probably dates back more than 3.5 billion years (57).
Conclusion
There is clear evidence from structural and functional studies that the peptide transporters that are driven by a transmembrane H+ gradient (POT family) are distinct from the peptide transporters that are directly energized by ATP (ABC peptide transporter family). The occurrence of H+-coupled peptide transport is much more widespread in nature than the occurrence of ATP-driven peptide transport. Several members of the POT family have been cloned from bacteria, yeast, plants, and animal tissues.
ACKNOWLEDGMENTS
This work was supported by NIH grant DK28389. We thank Ms. Lisa Young for excellent secretarial assistance.
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