title: The sticholysin family of pore-forming toxins induces the mixing of lipids in membrane domains.
abstract: Sticholysins (Sts) I and II (StI/II) are pore-forming toxins (PFTs) produced by the Caribbean Sea anemone Stichodactyla helianthus belonging to the actinoporin family, a unique class of eukaryotic PFTs exclusively found in sea anemones. The role of lipid phase co-existence in the mechanism of the action of membranolytic proteins and peptides is not clearly understood. As for actinoporins, it has been proposed that phase separation promotes pore forming activity. However little is known about the effect of sticholysins on the phase separation of lipids in membranes. To gain insight into the mechanism of action of sticholysins, we evaluated the effect of these proteins on lipid segregation using differential scanning calorimetry (DSC) and atomic force microscopy (AFM). New evidence was obtained reflecting that these proteins reduce line tension in the membrane by promoting lipid mixing. In terms of the relevance for the mechanism of action of actinoporins, we hypothesize that expanding lipid disordered phases into lipid ordered phases decreases the lipid packing at the borders of the lipid raft, turning it into a more suitable environment for N-terminal insertion and pore formation.
authors: Center for Protein Studies, Biology Faculty, University of Havana, Havana CP 10400, Cuba.
authors: Uris
authors: U
authors: Ros
authors: Michelle A
authors: MA
authors: Edwards
authors: Raquel F
authors: RF
authors: Epand
authors: Maria E
authors: ME
authors: Lanio
authors: Shirley
authors: S
authors: Schreier
authors: Christopher M
authors: CM
authors: Yip
authors: Carlos
authors: C
authors: Alvarez
authors: Richard M
authors: RM
authors: Epand
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D003064:Cnidarian Venoms / Q000494:pharmacology*; D008055:Lipids / Q000737:chemistry*; D021962:Membrane Microdomains / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D009930:Organic Chemicals / Q000494:pharmacology; D012615:Sea Anemones / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003064:Cnidarian Venoms; D008055:Lipids; D009930:Organic Chemicals; C404794:sticholysin II; C121348:stycholysin I
keywords: AFM; Actinoporin; Atomic Force Microscopy; Chol; DMPC; DOPC; DPPC; DSC; Differential Scanning Calorimetry; Dimyristoylphosphatidylcholine; Dioleoylphosphatidylcholine; Dipalmitoylphosphatidylcholine; EqtII; FraC; Ld; Lipid mixing; Lipid phase separation; Lo; MLV; PFTs; Pore-forming toxin; SM; SUV; Sphingomyelin; StI and StII; Sticholysin; T(m); Toroidal pore; calorimetric enthalpies; cholesterol; eSM; egg sphingomyelin; equinatoxin II; fragaceatoxin C; liquid-disordered domain; liquid-ordered domain; multilamellar vesicles; pore forming toxins; small unilamellar vesicles; sticholysin I and II; temperature of transition; ΔH