pH- and concentration-dependent supramolecular assembly of a fungal defensin plectasin variant into helical non-amyloid fibrils

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  • Christin Pohl
  • Gregory Effantin
  • Eaazhisai Kandiah
  • Sebastian Meier
  • Guanghong Zeng
  • Werner Streicher
  • Dorotea Raventos Segura
  • Per H. Mygind
  • Dorthe Sandvang
  • Line Anker Nielsen
  • Günther H.J. Peters
  • Guy Schoehn
  • Christoph Mueller-Dieckmann
  • Allan Noergaard
  • Harris, Pernille

Self-assembly and fibril formation play important roles in protein behaviour. Amyloid fibril formation is well-studied due to its role in neurodegenerative diseases and characterized by refolding of the protein into predominantly β-sheet form. However, much less is known about the assembly of proteins into other types of supramolecular structures. Using cryo-electron microscopy at a resolution of 1.97 Å, we show that a triple-mutant of the anti-microbial peptide plectasin, PPI42, assembles into helical non-amyloid fibrils. The in vitro anti-microbial activity was determined and shown to be enhanced compared to the wildtype. Plectasin contains a cysteine-stabilised α-helix-β-sheet structure, which remains intact upon fibril formation. Two protofilaments form a right-handed protein fibril. The fibril formation is reversible and follows sigmoidal kinetics with a pH- and concentration dependent equilibrium between soluble monomer and protein fibril. This high-resolution structure reveals that α/β proteins can natively assemble into fibrils.

OriginalsprogEngelsk
Artikelnummer3162
TidsskriftNature Communications
Vol/bind13
Udgave nummer1
ISSN2041-1723
DOI
StatusUdgivet - dec. 2022

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