The discovery of acanthaporin, a pore-forming protein from the parasite Acanthamoeba culbertsoni, is reported online this week in Nature Chemical Biology. The work explains how this pathogen attacks human cells and broadens our understanding of membrane insertion more generally.

Many pathogens contain toxins that act on the host cell membrane, forming pores or holes in the membrane that allow cellular contents to leak out, killing the cell. Matthias Leippe and colleagues show that the pore-forming protein acanthaporin, which can cause diseases such as encephalitis, uses a novel method to form pores. The structure contains a group of amino acid residues that are not charged at neutral pH, allowing the protein to form an inactive dimer, but become positively charged as the pH decreases, leading to a monomer that can come together into a ring of 6 proteins within the membrane. This unique structural transition makes the protein, and the parasite, even more toxic than the well known antimicrobial agent magainin.