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  • The EMBO Journal (2009) 28, 1332 - 1340
  • doi:10.1038/emboj.2009.65

Published online: 19 March 2009

The structural basis for peptide selection by the transport receptor OppA

Ronnie P-A Berntsson1, Mark K Doeven1, Fabrizia Fusetti1, Ria H Duurkens1, Durba Sengupta2, Siewert-Jan Marrink2, Andy-Mark W H Thunnissen2, Bert Poolman1 and Dirk-Jan Slotboom1

  1. Biochemistry Department, Groningen Biomolecular Sciences and Biotechnology Institute & Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands
  2. Biophysical Chemistry Department, Groningen Biomolecular Sciences and Biotechnology Institute & Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands

Correspondence to:

Dirk-Jan Slotboom, Biochemistry Department, Groningen Biomolecular Sciences and Biotechnology Institute & Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands. Tel.: +31 503634187; Fax: +31 503634165; E-mail: d.j.slotboom@rug.nl

Received 14 January 2009; Accepted 20 February 2009

Oligopeptide-binding protein A (OppA) from Lactococcus lactis binds peptides of an exceptionally wide range of lengths (4–35 residues), with no apparent sequence preference. Here, we present the crystal structures of OppA in the open- and closed-liganded conformations. The structures directly explain the protein's phenomenal promiscuity. A huge cavity allows binding of very long peptides, and a lack of constraints for the position of the N and C termini of the ligand is compatible with binding of peptides with varying lengths. Unexpectedly, the peptide's amino-acid composition (but not the exact sequence) appears to have a function in selection, with a preference for proline-rich peptides containing at least one isoleucine. These properties can be related to the physiology of the organism: L. lactis is auxotrophic for branched chain amino acids and favours proline-rich caseins as a source of amino acids. We propose a new mechanism for peptide selection based on amino-acid composition rather than sequence.

  • Keywords:

    • mass spectrometry,
    • peptide binding,
    • peptide transport,
    • X-ray crystallography