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Crystal structure of the water-soluble state of the pore-forming cytolysin Sticholysin II complexed with phosphorylcholineCrystal structure of the water-soluble state of the pore-forming cytolysin Sticholysin II complexed with phosphorylcholine
Structural highlights
FunctionACTP2_STIHL 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. Cytolytic effects include red blood cells hemolysis, platelet aggregation and lysis, cytotoxic and cytostatic effects on fibroblasts. Lethality in mammals has been ascribed to severe vasospasm of coronary vessels, cardiac arrhythmia, and inotropic effects.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSticholysin II (StnII) is a pore-forming protein (PFP) produced by the sea anemone Stichodactyla helianthus. We found out that StnII exists in a monomeric soluble state but forms tetramers in the presence of a lipidic interface. Both structures have been independently determined at 1.7 A and 18 A resolution, respectively, by using X-ray crystallography and electron microscopy of two-dimensional crystals. Besides, the structure of soluble StnII complexed with phosphocholine, determined at 2.4 A resolution, reveals a phospholipid headgroup binding site, which is located in a region with an unusually high abundance of aromatic residues. Fitting of the atomic model into the electron microscopy density envelope suggests that while the beta sandwich structure of the protein remains intact upon oligomerization, the N-terminal region and a flexible and highly basic loop undergo significant conformational changes. These results provide the structural basis for the membrane recognition step of actinoporins and unexpected insights into the oligomerization step. Crystal and electron microscopy structures of sticholysin II actinoporin reveal insights into the mechanism of membrane pore formation.,Mancheno JM, Martin-Benito J, Martinez-Ripoll M, Gavilanes JG, Hermoso JA Structure. 2003 Nov;11(11):1319-28. PMID:14604522[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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