9VNM

Cryo-EM structure of hnRAC1-2,8beta fibril polymorph1

Summary for 9VNM

• Entry DOI: 10.2210/pdb9vnm/pdb
• EMDB information: 65213
• Descriptor: GLY-SFE-GLY-GLY-ASN-ASP-ASN-SFE-GLY (1 entity in total)
• Functional Keywords: beta amino acid modified peptide, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 60
• Total formula weight: 53031.78

Authors

Li, Y.S.,Li, D.N.,Dai, B. (deposition date: 2025-06-30, release date: 2025-12-31)

Primary citation

Li, Y.,Li, D.,Yao, Y.,Liu, K.,Zhao, Q.,Zhang, Y.,Xu, Y.,Li, D.,Sun, B.,Liu, C.,Dai, B.
Conformational Adaptability and Thermostability in alpha / beta-Peptide Fibrils Induced by beta-Amino Acid Substitution.
Nano Lett., 2025

PubMed Abstract: The self-assembly of peptides into amyloid fibrils enables the design of functional biomaterials, yet the conformational constraints of α-peptides limit the attainable supramolecular diversity. Here, we introduce β-amino acids, β-phenylalanine (β-Phe), and β-homophenylalanine (β-hPhe) into the reversible fibril-forming core sequence hnRAC1 to generate α/β-peptide variants with distinct architectures and enhanced thermal stability. Cryo-EM reveals that β-modified peptides assemble into polymorphic fibrils with cross-β structures that differ markedly from each other and from native hnRAC1. Comparative structural analysis indicates that backbone extension by β-residues increases subunit conformational heterogeneity, enabling tighter packing and formation of more thermostable fibrils. Examination of intra- and intermolecular contacts shows that enhanced π-π stacking, hydrophobic interactions, hydrogen bonds, and electrostatic interactions likely contribute to fibril stabilization. These results show that minimal backbone modifications can remodel amyloid architecture, offering a generalizable strategy for designing structurally diverse and robust peptide-based biomaterials.

PubMed: 41420871
DOI: 10.1021/acs.nanolett.5c05223

Experimental method

ELECTRON MICROSCOPY (3.37 Å)