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

Pohl, ChristinLund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,Novozymes A/S,Technical University of Denmark (author)

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.

Effantin, GregoryUniversity Grenoble Alpes (author)
Kandiah, EaazhisaiEuropean Synchrotron Radiation Facility (author)
Meier, SebastianTechnical University of Denmark (author)
Zeng, GuanghongNovo Nordisk A/S,Danish National Metrology Institute (author)
Streicher, WernerNovozymes A/S (author)
Segura, Dorotea RaventosNovozymes A/S (author)
Mygind, Per H.Novozymes A/S (author)
Sandvang, DortheNovozymes A/S (author)
Nielsen, Line AnkerNovozymes A/S (author)
Peters, Günther H.J.Technical University of Denmark (author)
Schoehn, GuyUniversity Grenoble Alpes (author)
Mueller-Dieckmann, ChristophEuropean Synchrotron Radiation Facility (author)
Noergaard, AllanNovozymes A/S (author)
Harris, PernilleTechnical University of Denmark,University of Copenhagen (author)
Biokemi och StrukturbiologiCentrum för Molekylär Proteinvetenskap (creator_code:org_t)

By the author/editor: Pohl, Christin; Effantin, Gregor ...; Kandiah, Eaazhis ...; Meier, Sebastian; Zeng, Guanghong; Streicher, Werne ...; show more...; Segura, Dorotea ...; Mygind, Per H.; Sandvang, Dorthe; Nielsen, Line An ...; Peters, Günther ...; Schoehn, Guy; Mueller-Dieckman ...; Noergaard, Allan; Harris, Pernille; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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