1.C.38.1.8
Fragaceatoxin C (FraC) of the strawberry anemone (Structure solved to 1.8 Å resolution (PPDB acc # 4TSL); It is a crown-shaped nonamer with an external diameter of about 11.0 nm and an internal diameter of approximately 5.0 nm.) Almost identical to Equinatoxin II/Tenebrosin C (1.C.38.1.1) (Mechaly et al., 2011).  Fragaceatoxin C (FraC) is an α-barrel pore-forming toxin (PFT). The crystal structures of FraC at four different stages of the lytic mechanism have been determined at 3.1Å resolution, namely the water-soluble state, the monomeric lipid-bound form, an assembly intermediate and the fully assembled transmembrane pore (Tanaka et al. 2015). The structure of the transmembrane pore exhibits a unique architecture composed of both protein and lipids, with some of the lipids lining the pore wall, acting as assembly cofactors. The pore exhibits lateral fenestrations that expose the hydrophobic core of the membrane to the aqueous environment. The incorporation of lipids from the target membrane within the structure of the pore provides a membrane-specific trigger for the activation of this haemolytic toxin.  It has been reconstituted in  planar lipid bilayers and engineered for DNA analysis.  It shows a funnel-shaped geometry that allows tight wrapping around single-stranded DNA (ssDNA), resolving between homopolymeric C, T, and A polynucleotide stretches (Wloka et al. 2016). Despite the 1.2 nm internal constriction in the FraC pore, double-stranded DNA (dsDNA) can translocate through the nanopore at high applied potentials, presumably through deformation of the alpha-helical transmembrane region (Huang et al. 2017). Therefore, FraC nanopores might be useful for DNA sequencing and dsDNA analysis. Pore formation goes through a dimer intermediate and then generates the active octamer. Disrupting the key hydrophobic interaction between V60 and F163 (FraC numbering scheme) in the oligomerization interface of FraC, equinatoxin II (EqtII) and sticholysin II (StII) impairs the pore formation activity (Mesa-Galloso et al. 2016). It was reviewed by Gupta et al. 2023. FraE is almot identical to this protein.