Lipid Interactions Driving Actinoporin Pore Architecture and Stoichiometry

Actinoporins are pore-forming proteins from cnidarians that assemble into membrane-spanning complexes. Their preference for sphingomyelin-rich membranes and enhancement by cholesterol make them useful models of protein–lipid interactions. Gašper Šolinc will discuss the actinoporin-like protein Fav from Orbicella faveolata, whose funnel-shaped pores incorporate numerous lipids, with up to fifteen resolved lipids per subunit in the upper leaflet. The findings distinguish lipids involved in initial membrane binding from those stabilizing interfaces between protein subunits. Changing membrane composition yields different pore stoichiometries while preserving the protomer fold and lipid arrangement, linking membrane thickness and lipid composition to assembly. Comparisons with FraC and StnII structures address sphingomyelin recognition through hydrogen bonding and cation–π interactions, and why these pores are better understood as protein–lipid complexes.