7oae | pdb_00007oae
Cryo-EM structure of the plectasin fibril (double strands)
Structural highlights
FunctionDEFPL_PSENR Antimicrobial peptide that potently acts against several species of Gram-positive bacteria (PubMed:16222292, PubMed:19472324). It selectively inhibits peptidoglycan biosynthesis through complex formation with the cell wall precursor lipid II (1:1 molar ratio) thus inhibiting cell wall synthesis (PubMed:20508130). It does not disrupt cell membranes (PubMed:20508130). Is especially active against numerous clinical isolates of S.pneumoniae, including all 90 different serotypes and isolates resistant to clinically used antibiotics (PubMed:16222292). In vitro, shows considerable selectivity for bacteria over mammalian cells (PubMed:16222292). The peptide synthesized in D-amino acids does not show antibacterial activity (PubMed:19472324). In vitro, acts on voltage-gated potassium channels by moderately inhibiting mammalian Kv1.3/KCNA3 (IC(50)=2.8 uM), and moderately inhibiting others potassium channels (PubMed:25568977).[1] [2] Publication Abstract from PubMedSelf-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 beta-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 A, 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 alpha-helix-beta-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 alpha/beta proteins can natively assemble into fibrils. pH- and concentration-dependent supramolecular assembly of a fungal defensin plectasin variant into helical non-amyloid fibrils.,Pohl C, Effantin G, Kandiah E, Meier S, Zeng G, Streicher W, Segura DR, Mygind PH, Sandvang D, Nielsen LA, Peters GHJ, Schoehn G, Mueller-Dieckmann C, Noergaard A, Harris P Nat Commun. 2022 Jun 7;13(1):3162. doi: 10.1038/s41467-022-30462-w. PMID:35672293[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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