title: Investigating the Structural Variability and Binding Modes of the Glioma Targeting NFL-TBS.40-63 Peptide on Tubulin.
abstract: NFL-TBS.40-63 is a 24 amino acid peptide corresponding to the tubulin-binding site located on the light neurofilament subunit, which selectively enters glioblastoma cells, where it disrupts their microtubule network and inhibits their proliferation. We investigated its structural variability and binding modes on a tubulin heterodimer using a combination of NMR experiments, docking, and molecular dynamics (MD) simulations. Our results show that, while lacking a stable structure, the peptide preferentially binds on a specific single site located near the β-tubulin C-terminal end, thus giving us precious hints regarding the mechanism of action of the NFL-TBS.40-63 peptide's antimitotic activity at the molecular level.
authors.affiliation: †Laboratoire de Biochimie Théorique, UPR 9080 CNRS Institut de Biologie Physico-Chimique,13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Laurin
authors.affiliation: ‡Université Paris 13, Sorbonne Paris Cité, CSPBAT, UMR 7244 CNRS, 74 rue Marcel Cachin, 93017 Bobigny, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Savarin
authors.affiliation: †Laboratoire de Biochimie Théorique, UPR 9080 CNRS Institut de Biologie Physico-Chimique,13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Robert
authors.affiliation: §School of Bioscience and Biotechnology, Tokyo Institue of Technology 2-12-1-M6-14 Ookayama, Meguro-ku, Tokyo 152-8550 Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Joel
authors.initials: J
authors.lastname: Eyer
authors.affiliation: †Laboratoire de Biochimie Théorique, UPR 9080 CNRS Institut de Biologie Physico-Chimique,13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Prevost
authors.affiliation: †Laboratoire de Biochimie Théorique, UPR 9080 CNRS Institut de Biologie Physico-Chimique,13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sacquin-Mora
mesh_terms: D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D016900:Neurofilament Proteins / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D017433:Protein Structure, Secondary; D012995:Solubility; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; C576937:NFL-TBS.40-63 peptide; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D014404:Tubulin