Disrupting a key hydrophobic pair in the oligomerization interface of the actinoporins impairs their pore‐forming activity

• DOI: 10.1002/pro.3104
• Publication Date: 2016-12-21T08:56:48Z
• Authors: Haydeé Mesa‐Galloso; Karelia H. Delgad...; Sheila Cabezas; Aracelys López‐Ca...; Jorge E. Hernánde...; Lohans Pedrera; Carlos Alvarez; D. Peter Tieleman; Ana J. García‐Sáez; Maria E. Lanio; Uris Ros; Pedro A. Valiente
• Keywords: Hydrophobic effect

Crystallographic data of the dimeric and octameric forms fragaceatoxin C (FraC) suggested key role a small hydrophobic protein-protein interaction surface for actinoporins oligomerization pore formation in membranes. However, site-directed mutagenesis studies supporting this hypothesis others are still lacking. Here, we demonstrate that disrupting between V60 F163 (FraC numbering scheme) interface FraC, equinatoxin II (EqtII), sticholysin (StII) impairs activity these proteins. Our results allow extension importance FraC interactions stabilization oligomeric intermediates StII EqtII pointing out all proteins follow similar pathway membrane disruption. These findings support hybrid proposal as universal model formation. Moreover, reinforce relevance dimer formation, which appears to be functional intermediate assembly some different pore-forming