Proton-dependent oligopeptide transporter explained

Proteins of the Proton-dependent Oligopeptide Transporter (POT) Family (also called the PTR (peptide transport) family) are found in animals, plants, yeast, archaea and both Gram-negative and Gram-positive bacteria, and are part of the major facilitator superfamily. The transport of peptides into cells is a well-documented biological phenomenon which is accomplished by specific, energy-dependent transporters found in a number of organisms as diverse as bacteria and humans. The proton-dependent oligopeptide transporter (PTR) family of proteins is distinct from the ABC-type peptide transporters and was uncovered by sequence analyses of a number of recently discovered peptide transport proteins.[1] These proteins that seem to be mainly involved in the intake of small peptides with the concomitant uptake of a proton.[2]

Function

While most members of the POT family catalyze peptide transport, one is a nitrate permease and one can transport histidine, as well as peptides. Some of the peptide transporters can also transport antibiotics. They function by proton symport, but the substrate:H+ stoichiometry is variable: the high-affinity rat PepT2 carrier catalyzes uptake of 2 and 3 H+ with neutral and anionic dipeptides, respectively, while the low affinity PepT1 carrier catalyzes uptake of one H+ per neutral peptide.[3] [4]

Transport Reaction

The generalized transport reaction catalyzed by the proteins of the POT family is:

substrate (out) + H (out) → substrate (in) H+ (in)

Structure and Mechanism

The proteins are of about 450-600 amino acyl residues in length with the eukaryotic proteins in general being longer than the bacterial proteins. They exhibit 12 putative or established transmembrane α-helical spanners.

Pairs of salt bridge interactions between transmembrane helices work in tandem to orchestrate alternating access transport within the PTR family.[5] Key roles for residues conserved between bacterial and eukaryotic homologues suggest a conserved mechanism of peptide recognition and transport that in some cases has been subtly modified in individual species.

Human proteins containing this domain

FP12591

PEPT1; PTR4; SLC15A1; SLC15A2; SLC15A3; SLC15A4; hPEPT1-RF;

Notes and References

  1. Naider F, Becker JM, Steiner HY . The PTR family: a new group of peptide transporters . Mol. Microbiol. . 16 . 5 . 825–834 . 1995 . 7476181 . 10.1111/j.1365-2958.1995.tb02310.x. 46360416 . free .
  2. Skurray RA, Paulsen IT . The POT family of transport proteins . Trends Biochem. Sci. . 19 . 10 . 404 . 1994 . 7817396 . 10.1016/0968-0004(94)90087-6.
  3. Bucking, Carol. Schulte, Patricia M.. Patricia Schulte.
  4. Chen. Xing-Zhen. 29 Jan 1999. Stoichiometry and kinetics of the high-affinity H+-coupled peptide transporter PepT2.. Journal of Biological Chemistry. 274. 5. 2773–2779. 10.1074/jbc.274.5.2773. 9915809. free.
  5. Doki. Shintaro. Kato. Hideaki E.. Solcan. Nicolae. Iwaki. Masayo. Koyama. Michio. Hattori. Motoyuki. Iwase. Norihiko. Tsukazaki. Tomoya. Sugita. Yuji. 2013-07-09. Structural basis for dynamic mechanism of proton-coupled symport by the peptide transporter POT. Proceedings of the National Academy of Sciences of the United States of America. 110. 28. 11343–11348. 10.1073/pnas.1301079110. 1091-6490. 3710879. 23798427. 2013PNAS..11011343D. free.