Atomic structures of naphthalene dipeptide micelles unravel mechanisms of assembly and gelation

Sonani, R. R., Bianco, S. , Dietrich, B. , Doutch, J., Draper, E. R. , Adams, D. J. and Egelman, E. H. (2024) Atomic structures of naphthalene dipeptide micelles unravel mechanisms of assembly and gelation. Cell Reports Physical Science, 5(2), 101812. (doi: 10.1016/j.xcrp.2024.101812)

Abstract

Peptide-based biopolymers have gained increasing attention due to their versatile applications. A naphthalene dipeptide (2NapFF) can form chirality-dependent tubular micelles, leading to supramolecular gels. The precise molecular arrangement within these micelles and the mechanism governing gelation have remained enigmatic. We determined, at near-atomic resolution, cryoelectron microscopy structures of the 2NapFF micelles LL-tube and LD-tube, generated by the stereoisomers (ʟ,ʟ)-2NapFF and (ʟ,ᴅ)-2NapFF, respectively. The structures reveal that the fundamental packing of dipeptides is driven by the systematic π-π stacking of aromatic rings and that same-charge repulsion between the carbonyl groups is responsible for the stiffness of both tubes. The structural analysis elucidates how a single residue’s altered chirality gives rise to markedly distinct tubular structures and sheds light on the mechanisms underlying the pH-dependent gelation of LL- and LD-tubes. The understanding of dipeptide packing and gelation mechanisms provides insights for the rational design of 2NapFF derivatives, enabling the modulation of micellar dimensions.

• Item Type: Articles
• Additional Information: DA thanks the EPSRC for a Fellowship (EP/L021 978/2) which also funded BD. ED thanks the UKRI (MR/V021087/1) for funding a Future Leaders Fellowship. HE was funded by NIH grant GM122510.
• Keywords: cryo-electron Microscopy, π- π stacking, stereoisomers, supramolecular gels, gelators.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dietrich, Bart and Draper, Emily and Bianco, Simona and Adams, Dave
• Authors: Sonani, R. R., Bianco, S., Dietrich, B., Doutch, J., Draper, E. R., Adams, D. J., and Egelman, E. H.
• College/School: College of Science and Engineering; College of Science and Engineering > School of Chemistry
• Journal Name: Cell Reports Physical Science
• Publisher: Elsevier (Cell Press)
• ISSN: 2666-3864
• ISSN (Online): 2666-3864
• Copyright Holders: Copyright: © 2024 The Author(s)
• First Published: First published in Cell Reports Physical Science 5(2): 101812
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
174004		Multicomponent Supramolecular Hydrogels	Dave Adams	Engineering and Physical Sciences Research Council (EPSRC)	EP/L021978/2	Chemistry