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Updated: Nov 14, 2025
Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Specific inhibition of the Survivin-CRM1 interaction by peptide-modified molecular tweezers
Annika Meiners1, Sandra Bäcker1, Inesa Hadrović2
1Department of Molecular Biology II, Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.
Abstract:
Survivin's dual function as apoptosis inhibitor and regulator of cell proliferation is mediated via its interaction with the export receptor CRM1. This protein-protein interaction represents an attractive target in cancer research and therapy. Here, we report a sophisticated strategy addressing Survivin's nuclear export signal (NES), the binding site of CRM1, with advanced supramolecular tweezers for lysine and arginine. These were covalently connected to small peptides resembling the natural, self-complementary dimer interface which largely overlaps with the NES. Several biochemical methods demonstrated sequence-selective NES recognition and interference with the critical receptor interaction. These data were strongly supported by molecular dynamics simulations and multiscale computational studies. Rational design of lysine tweezers equipped with a peptidic recognition element thus allowed to address a previously unapproachable protein surface area. As an experimental proof-of-principle for specific transport signal interference, this concept should be transferable to any protein epitope with a flanking well-accessible lysine.
Insights
Researchers developed supramolecular tweezers to block Survivin
Area of Science:
- Biochemistry
- Molecular Biology
- Chemical Biology
Background:
- Survivin is a key protein regulating apoptosis and cell proliferation.
- Survivin's interaction with the export receptor CRM1 is crucial for its function and a target for cancer therapy.
- The nuclear export signal (NES) of Survivin is the binding site for CRM1.
Purpose of the Study:
- To develop a novel strategy to inhibit Survivin-CRM1 interaction.
- To target Survivin's nuclear export signal (NES) using advanced molecular tools.
Main Methods:
- Design and synthesis of supramolecular tweezers with peptidic recognition elements.
- Biochemical assays to demonstrate sequence-selective NES recognition.
- Molecular dynamics simulations and multiscale computational studies.
Main Results:
- The developed supramolecular tweezers specifically recognized Survivin's NES.
- Interference with the critical Survivin-CRM1 receptor interaction was demonstrated.
- Computational studies supported the experimental findings.
Conclusions:
- Supramolecular tweezers offer a novel approach to target protein-protein interactions.
- This strategy provides a proof-of-principle for specific interference with nuclear export signals.
- The concept is potentially transferable to other protein epitopes with accessible lysine residues.
