9D70

Cryo-EM of helical fibers formed by two peptides Pyn-K6 and Pyn-(EY)3

Summary for 9D70

• Entry DOI: 10.2210/pdb9d70/pdb
• EMDB information: 46599
• Descriptor: PYR-K6, PYR-EY3, (pyren-1-yl)acetic acid (3 entities in total)
• Functional Keywords: peptide fiber, heterotypic peptide, helical polymer, protein fibril
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 2432.80

Authors

Zia, A.,Qiao, Y.,Xu, B.,Wang, F. (deposition date: 2024-08-16, release date: 2025-01-22, Last modification date: 2025-02-12)

Primary citation

Qiao, Y.,Zia, A.,Wu, G.,Liu, Z.,Guo, J.,Chu, M.,He, H.,Wang, F.,Xu, B.
Context-Dependent Heterotypic Assemblies of Intrinsically Disordered Peptides.
J.Am.Chem.Soc., 147:2978-2983, 2025

PubMed Abstract: Despite their critical role in context-dependent interactions for protein functions, intrinsically disordered regions (IDRs) are often overlooked for designing peptide assemblies. Here, we exploit IDRs to enable context-dependent heterotypic assemblies of intrinsically disordered peptides, where "context-dependent" refers to assembly behavior driven by interactions with other molecules. By attaching an aromatic segment to oppositely charged intrinsically disordered peptides, we achieve a nanofiber formation. Although the same-charged peptides cannot self-assemble, oppositely charged peptides form heterotypic nanofibers. Cryo-EM analysis reveals a β-sheet arrangement within the ordered core of these nanofibers, conformational heterogeneity, and a disorder-to-order continuum and shows a high number of hydrogen bonds between tyrosine and lysine ε-amine. Additionally, this work demonstrates a post-assembly morphological change resulting from local conformational flexibility. While equal molar mixtures of the charged intrinsically disordered peptides yield nanofibers, doubling the positively charged peptides after assembly produces bundles of nanofibers. Furthermore, reducing the number of aromatic amino acid residues reduces bundle formation. Demonstrating context-dependent self-assembly of intrinsically disordered peptides and revealing atomistic insights into heterotypic assemblies of intrinsically disordered peptides for the first time, this work illustrates a straightforward approach to enable heterotypic intrinsically disordered peptides to self-assemble for the design of adaptive, multifunctional peptide nanomaterials.

PubMed: 39808585
DOI: 10.1021/jacs.4c12150

Experimental method

ELECTRON MICROSCOPY (3.3 Å)