Identifying Heterozipper β-Sheet in Twisted Amyloid Aggregation

Yongxiu Song, Bin Dai, Yong Wang, Yin Wang, Cong Liu, Pontus Gourdon, Lei Liu*, Kaituo Wang, Mingdong Dong

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

9 Citations (Scopus)

Abstract

Amyloid peptide (AP) self-assembly is a hierarchical process. However, the mechanistic rule of guiding peptides to organize well-ordered nanostructure in a clear and precise manner remains poorly understood. Herein we explored the molecular insight of AP motif aggregates underlying hierarchical process with helical fibrillar structure by atomic force microscope, cryo-electron microscopy (cryo-EM), and molecular dynamics simulation. AP assembly encompasses well-ordered twisted fibrils with uniform morphology, size, and periodicity. More importantly, a heterozipper β-sheet was identified in a protofilament of AP assembly determined by cryo-EM with a high resolution of 3.5 Å. Each peptide heterozipper was further composed of two antiparallel β strands and arranged by an alternative manner in a protofilament. The hydrophobic core and hydrophilic area in each zipper played the significant role for peptide assembling. This work proposed and verified the rule facilitating the basic building unit to form twisted fibrils and gave the explanation of peptide hierarchical assembling.

Original languageEnglish
JournalNano Letters
Volume22
Issue number9
Pages (from-to)3707–3712
ISSN1530-6984
DOIs
Publication statusPublished - 2022

Bibliographical note

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Keywords

  • atomic force microscopy
  • cryo-electron microscopy (cryo-EM)
  • hierarchical nanostructure
  • peptide self-assembly
  • twisted nanofibrils

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