Journal article
pH- and concentration-dependent supramolecular assembly of a fungal defensin plectasin variant into helical non-amyloid fibrils
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.
Language: | English |
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Publisher: | Nature Publishing Group UK |
Year: | 2022 |
Pages: | 3162 |
ISSN: | 20411723 |
Types: | Journal article |
DOI: | 10.1038/s41467-022-30462-w |
ORCIDs: | 0000-0001-6193-4016 , 0000-0002-6957-0875 , 0000-0002-9877-7621 , Meier, Sebastian , Peters, Günther H.J. , 0000-0002-1459-3201 , 0000-0003-1850-9879 and Harris, Pernille |