Anatomy of a selectively coassembled β-sheet peptide nanofiber

Qing Shao, Kong M. Wong, Dillon T. Seroski, Yiming Wang, Renjie Liu, Anant K. Paravastu, Gregory A. Hudalla, Carol K. Hall

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Peptide self-assembly, wherein molecule A associates with other A molecules to form fibrillar β-sheet structures, is common in nature and widely used to fabricate synthetic biomaterials. Selective coassembly of peptide pairs A and B with complementary partial charges is gaining interest due to its potential for expanding the form and function of biomaterials that can be realized. It has been hypothesized that charge-complementary peptides organize into alternating ABAB-type arrangements within assembled β-sheets, but no direct molecular-level evidence exists to support this interpretation. We report a computational and experimental approach to characterize molecular-level organization of the established peptide pair, CATCH. Discontinuous molecular dynamics simulations predict that CATCH(+) and CATCH(−) peptides coassemble but do not self-assemble. Two-layer β-sheet amyloid structures predominate, but off-pathway β-barrel oligomers are also predicted. At low concentration, transmission electron microscopy and dynamic light scattering identified nonfibrillar ∼20-nm oligomers, while at high concentrations elongated fibers predominated. Thioflavin T fluorimetry estimates rapid and near-stoichiometric coassembly of CATCH(+) and CATCH(−) at concentrations ≥100 μM. Natural abundance 13C NMR and isotope-edited Fourier transform infrared spectroscopy indicate that CATCH(+) and CATCH(−) coassemble into two-component nanofibers instead of self-sorting. However, 13C-13C dipolar recoupling solid-state NMR measurements also identify nonnegligible AA and BB interactions among a majority of AB pairs. Collectively, these results demonstrate that strictly alternating arrangements of β-strands predominate in coassembled CATCH structures, but deviations from perfect alternation occur. Off-pathway β-barrel oligomers are also suggested to occur in coassembled β-strand peptide systems.

Original languageEnglish
Pages (from-to)4710-4717
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number9
DOIs
StatePublished - Mar 3 2020

Bibliographical note

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.

Keywords

  • Coarse-grained simulation
  • Coassembly
  • Fibril
  • Peptides
  • β-barrel

ASJC Scopus subject areas

  • General

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