Multispecific Substrate Recognition in a Proton-Dependent Oligopeptide Transporter

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Maria Martinez Molledo, Centre for Structural Systems Biology (CSSB), DESY and European Molecular Biology Laboratory Hamburg, Notkestrasse 85, 22607 Hamburg, Germany.
  • ,
  • Esben M Quistgaard
  • Ali Flayhan, Centre for Structural Systems Biology (CSSB), DESY and European Molecular Biology Laboratory Hamburg, Notkestrasse 85, 22607 Hamburg, Germany.
  • ,
  • Joanna Pieprzyk, Centre for Structural Systems Biology (CSSB), DESY and European Molecular Biology Laboratory Hamburg, Notkestrasse 85, 22607 Hamburg, Germany.
  • ,
  • Christian Löw, Centre for Structural Systems Biology (CSSB), DESY and European Molecular Biology Laboratory Hamburg, Notkestrasse 85, 22607 Hamburg, Germany; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 17177 Stockholm, Sweden. Electronic address: christian.loew@embl-hamburg.de.

Proton-dependent oligopeptide transporters (POTs) are important for uptake of dietary di- and tripeptides in many organisms, and in humans are also involved in drug absorption. These transporters accept a wide range of substrates, but the structural basis for how different peptide side chains are accommodated has so far remained obscure. Twenty-eight peptides were screened for binding to PepTSt from Streptococcus thermophilus, and structures were determined of PepTSt in complex with four physicochemically diverse dipeptides, which bind with millimolar affinity: Ala-Leu, Phe-Ala, Ala-Gln, and Asp-Glu. The structures show that PepTSt can adapt to different peptide side chains through movement of binding site residues and water molecules, and that a good fit can be further aided by adjustment of the position of the peptide itself. Finally, structures were also determined in complex with adventitiously bound HEPES, polyethylene glycol, and phosphate molecules, which further underline the adaptability of the binding site.

Original languageEnglish
JournalStructure
Volume26
Issue3
Pages (from-to)467-476.e4
ISSN0969-2126
DOIs
Publication statusPublished - 6 Mar 2018
Externally publishedYes

See relations at Aarhus University Citationformats

ID: 141501723