Séminaire du 8 juin 2023

Molecular-scale resolution of the structure of short peptides-based nanofiber by cryo-electron microscopy image reconstruction

Alexis Bigo-Simon, Chimie de la Matière Complexe (UMR 7140), Institut Charles Sadron (UPR 22)

Résumé :Cryo-electronic microscopy reconstruction techniques are tremendiously used to resolve the structure of viruses or even smaller entities such as proteins. Very recently, these approches have also been succesfully applied to elucidate the spatial organisation of nanostrutures based on oligo or polypeptides assemblies[1]. Following this line, the next challenge would be to elucidate the molecular scale organization of nanostructures based on very short peptides assemblies (i.e. peptides containing up to three residues) since this kind of buiding blocks displays no secondary structures such as α-helix or β-sheet organization for which the outcome prediction of their assembly is not obvious. In addition, these very short peptide assemblies have recently been shown as particularly appealing for bioimaging, anticancer therapy, theranostic strategy or drug delivery:[2] the understanding of their molecular scale structure would be highly interesting for the optimization of peptides sequence for various biomedical applications. Using high resolution of cryo-TEM images and tools such as RELION and crYOLO, we have obtained a density map of 3.8 Å of resolution from a tripeptide-assembled nanofiber (tripeptide sequence: Fmoc-FFY), as shown in Figure 1. Thus, a suitable correlation between this map and the molecular structure of the tripeptide resulted in the determination of the nanofiber structure at the molecular scale. The fitted model was used as a starting situation for molecular dynamics (MD) investigations highlighting the interactions ensuring the cohesion of the supramolecular architecture. Informations obtained from experimental studies (IR, CD, SAXS, Fluorescence) are in full agreement with our so-resolved nanofiber structure. In this presentation, the reconstruction, the MD simulations and the comparison with experimental data will be shown and discussed.