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Identifying Heterozipper β-Sheet in Twisted Amyloid Aggregation

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  • Yongxiu Song, University of Chinese Academy of Sciences, Jiangsu University
  • ,
  • Bin Dai, Shanghai Jiao Tong University
  • ,
  • Yong Wang, The Provincial International Science and Technology Cooperation Base on Engineering Biology, Zhejiang University
  • ,
  • Yin Wang
  • ,
  • Pontus Gourdon, University of Copenhagen, Lund University
  • ,
  • Lei Liu, Jiangsu University
  • ,
  • Kaituo Wang, Department of Biomedical Sciences, University of Copenhagen
  • ,
  • Mingdong Dong

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
Pages (from-to)3707-3712
Publication statusPublished - 11 May 2022

Bibliographical note

Funding Information:
The authors thank the National Natural Science Foundation of China (22072060, 21573097), Independent Research Fund Denmark, EU H2020RISE 2016-MNR4S Cell project, Zhejiang Province Post-Doctoral Scientific Research Fund (269745) for financial support. We also thank Nykola Jones in the Department of Physics and Astronomy Centre for Storage Ring Facilities (ISA) for her expertise and help in Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy experiment.

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    Research areas

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

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