Structure-based synthetic mimicry of discontinuous protein binding sites: inhibitors of the interaction of Mena EVH1 domain with proline-rich ligands

Chembiochem : a European Journal of Chemical Biology
Cornelia HunkeJutta Eichler

Abstract

The Mena EVH1 domain, a protein-interaction module involved in actin-based cell motility, recognizes proline-rich ligand motifs, which are also present in the sequence of the surface protein ActA of Listeria monocytogenes. The interaction of ActA with host Mena EVH1 enables the bacterium to actively recruit host actin in order to spread into neighboring cells. Based on the crystal structure of Mena EVH1 in complex with a polyproline peptide ligand, we have generated a range of assembled peptides presenting the Mena EVH1 fragments that make up its discontinuous binding site for proline-rich ligands. Some of these peptides were found to inhibit the interaction of Mena EVH1 with the ligand pGolemi. One of them was further characterized at the level of individual amino acid residues; this yielded information on the contribution of individual positions of the peptides to the interaction with the ligand and identified sites for future structure optimization.

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Citations

Jan 12, 2013·Current Protein & Peptide Science·Rita Berisio, Luigi Vitagliano
Apr 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Robert OpitzRonald Kühne
Oct 22, 2008·Current Opinion in Chemical Biology·Jutta Eichler

Related Concepts

ActA protein, Listeria monocytogenes
Bacterial Proteins
Ligands
Listeria monocytogenes
Cell Surface Proteins
Proline
Plasma Protein Binding Capacity
Tertiary Protein Structure
Molecular Mimicry
Inhibitory Concentration 50

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