Architecture of the pore forming toxin sticholysin I in membranes

• Published in: Journal of structural biology Vol. 208; no. 1; pp. 30 - 42
• Main Authors: Hervis, Yadira P., Valle, Aisel, Dunkel, Sabrina, Klare, Johann P., Canet, Liem, Lanio, Maria E., Alvarez, Carlos, Pazos, Isabel F., Steinhoff, Heinz-J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Actinoporins; EPR spectroscopy; Oligomerization; Pore-forming toxins; Site-directed spin labeling; Sticholysin; MTSSL; Site-directed spin labeling; CF; Ni-EDDA; Oligomerization; StII; mem-StI; RLA; Sticholysin; EqtII; StI; LUV; FraC; DEER; Pore-forming toxins; sol-StI; POPC; Actinoporins; SM; EPR spectroscopy
• ISSN: 1047-8477; 1095-8657
• DOI: 10.1016/j.jsb.2019.07.008

[Display omitted] •The topology of membrane bound StI resembles a conical pore model.•Membrane bound StI adopts ‘pre-pore’ and ‘pore’ conformations.•StI forms oligomers of heterogeneous stoichiometry in the membrane. Sticholysin I (StI) is a toxin produced by the sea anemone Stichodactyla helianthus and belonging to the actinoporins family. Upon binding to sphingomyelin-containing membranes StI forms oligomeric pores, thereby leading to cell death. According to recent controversial experimental evidences, the pore architecture of actinoporins is a debated topic. Here, we investigated the StI topology in membranes by site-directed spin labeling and electron paramagnetic resonance spectroscopy. The results reveal that StI in membrane exhibits an oligomeric architecture with heterogeneous stoichiometry of predominantly eight or nine protomers, according to the available structural models. The StI topology resembles the conic pore structure reported for the actinoporin fragaceatoxin C. Our data show that StI coexists in two membrane-associated conformations, with the N-terminal segment either attached to the protein core or inserted in the membrane forming the pore. This finding suggests a ‘pre-pore’ to ‘pore’ transition determined by a conformational change that detaches the N-terminal segment.