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

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, Pernille Harris*

*Corresponding author for this work

Research output: Contribution to journalLetterResearchpeer-review

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Abstract

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.
Original languageEnglish
Article number3162
JournalNature Communications
Volume13
Number of pages15
ISSN2041-1723
DOIs
Publication statusPublished - 2022

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