pH- and concentration-dependent supramolecular assembly of a fungal defensin plectasin variant into helical non-amyloid fibrils
(2022) In Nature Communications 13(1).- 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.... (More)
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.
(Less)
- author
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 13
- issue
- 1
- article number
- 3162
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85131487477
- pmid:35672293
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-022-30462-w
- language
- English
- LU publication?
- yes
- id
- c8ff9a70-41f5-49de-b675-b2ed5c57a483
- date added to LUP
- 2022-09-30 15:26:49
- date last changed
- 2024-06-23 19:34:44
@article{c8ff9a70-41f5-49de-b675-b2ed5c57a483,
abstract = {{<p>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.</p>}},
author = {{Pohl, Christin and Effantin, Gregory and Kandiah, Eaazhisai and Meier, Sebastian and Zeng, Guanghong and Streicher, Werner and Segura, Dorotea Raventos and Mygind, Per H. and Sandvang, Dorthe and Nielsen, Line Anker and Peters, Günther H.J. and Schoehn, Guy and Mueller-Dieckmann, Christoph and Noergaard, Allan and Harris, Pernille}},
issn = {{2041-1723}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{pH- and concentration-dependent supramolecular assembly of a fungal defensin plectasin variant into helical non-amyloid fibrils}},
url = {{http://dx.doi.org/10.1038/s41467-022-30462-w}},
doi = {{10.1038/s41467-022-30462-w}},
volume = {{13}},
year = {{2022}},
}