9gkp
From Proteopedia
Structure of fragacetoxin C in lipid nanodiscs
Structural highlights
FunctionACTPC_ACTFR Pore-forming protein that forms cations-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and hemolysis. Pore formation is a multi-step process that involves specific recognition of membrane sphingomyelin (but neither cholesterol nor phosphatidylcholine) using aromatic rich region and adjacent phosphocholine (POC) binding site, firm binding to the membrane (mainly driven by hydrophobic interactions) accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of several monomers.[1] Publication Abstract from PubMedPore-forming proteins exemplify the transformative potential of biological molecules. Produced as soluble monomers, they assemble into multimeric membrane-inserted complexes in response to specific membrane environments. Actinoporins, a class of pore-forming proteins from sea anemones, target membranes to kill cells. Here, we report cryogenic electron microscopy structures of two actinoporins, fragaceatoxin C and sticholysin II, reconstituted in lipid membranes. The structures reveal an ordered arrangement of dozens of lipid molecules that form an integral part of the pore architecture. We also captured distinct oligomeric intermediates, arc-shaped assemblies with monomers in transitional conformations, representing key snapshots along the pore formation pathway. These data provide direct structural evidence for a stepwise mechanism in which monomers sequentially bind the membrane and undergo conformational changes that drive pore assembly and membrane disruption. Our findings reveal how these proteins reshape membranes and offer mechanistic insights into their cytolytic activity. This work broadens our understanding of pore-forming proteins, which are gaining increasing relevance in diverse biotechnological applications. Elucidating the structure and assembly mechanism of actinoporin pores in complex membrane environments.,Arranz R, Santiago C, Masiulis S, Rivera-de-Torre E, Palacios-Ortega J, Carlero D, Heras-Marquez D, Gavilanes JG, Arias-Palomo E, Martinez-Del-Pozo A, Garcia-Linares S, Martin-Benito J Sci Adv. 2025 Sep 26;11(39):eadv0683. doi: 10.1126/sciadv.adv0683. Epub 2025 Sep , 24. PMID:40991702[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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