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Membrane Transport Mechanism pp 159–179Cite as

Alternating Access Within the POT Family of Oligopeptide Proton Symporters

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Part of the book series: Springer Series in Biophysics ((BIOPHYSICS,volume 17))

Abstract

The POT family of proton-dependent oligopeptide transporters belongs to the Major Facilitator Superfamily and is widely distributed within prokaryotic and eukaryotic kingdoms. They function as proton:peptide symporters, using the inwardly directed proton electrochemical gradient to drive the uptake of di- and tripeptides into the cell. Mammals contain two members of the POT family, PepT1 and PepT2, which in addition to their physiological role in peptide import also recognise and transport several important drug families, including the β-lactam antibiotics and a growing library of peptide modified pro-drugs. A detailed molecular understanding of peptide recognition and transport within the POT family therefore has an acute medical significance that crystallographic methods are now uniquely placed to address. In the last few years the crystal structures of two prokaryotic POT family transporters have been determined, one with bound ligand. These structures represent key intermediates in the transport cycle and reveal remarkably well-conserved sequence and structural motifs that impact peptide specificity and transport rates. However, key questions remain to be answered, including the site(s) and role of protonation and peptide binding in orchestrating the structural changes that result in transport. In this chapter we discuss the insights recent crystal structures of bacterial POT family transporters have provided and examine how these questions are being addressed.

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  1. Department of Biochemistry, University of Oxford, Oxford, UK

    Simon Newstead

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  1. Simon Newstead
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Correspondence to Simon Newstead .

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Editors and Affiliations

  1. Department Chemistry Institute of Biochemistry, University of Cologne, Köln, Germany

    Reinhard Krämer

  2. Faculty for Biology and Preclinical Medicine, University of Regensburg, Regensburg, Germany

    Christine Ziegler

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Newstead, S. (2014). Alternating Access Within the POT Family of Oligopeptide Proton Symporters. In: Krämer, R., Ziegler, C. (eds) Membrane Transport Mechanism. Springer Series in Biophysics, vol 17. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-53839-1_7

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  • DOI: https://doi.org/10.1007/978-3-642-53839-1_7

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