2NH and 3OH are crucial structural requirements in sphingomyelin for sticholysin II binding and pore formation in bilayer membranes.

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RESEARCH PRODUCT

2NH and 3OH are crucial structural requirements in sphingomyelin for sticholysin II binding and pore formation in bilayer membranes.

Mayuko Kurita J. Peter Slotte Y. Jenny E. Isaksson Shigeo Katsumura Sanna Niinivehmas ÁLvaro Martínez-del-pozo Tetsuya Yamamoto José G. Gavilanes Shou Yamaguchi Sara García-linares Terhi Maula Olli T. Pentikäinen

subject

Models Molecular Pore Forming Cytotoxic Proteins Membrane permeabilization Lipid Bilayers Biophysics Calorimetry ta3111 Biochemistry chemistry.chemical_compound Cnidarian Venoms Animals Computer Simulation Lipid bilayer ta116 Binding selectivity Unilamellar Liposomes Phosphocholine Binding Sites Molecular Structure Chemistry Hydrogen bond Vesicle ta1182 Isothermal titration calorimetry Hydrogen Bonding Cell Biology Surface Plasmon Resonance Protein Structure Tertiary Sphingomyelins Kinetics Membrane Sea Anemones Biochemistry Molecular docking Isothermal titration calorimetry Biophysics Phosphatidylcholines Sphingomyelin Protein Binding

description

AbstractSticholysin II (StnII) is a pore-forming toxin from the sea anemone Stichodactyla heliantus which belongs to the large actinoporin family. The toxin binds to sphingomyelin (SM) containing membranes, and shows high binding specificity for this lipid. In this study, we have examined the role of the hydrogen bonding groups of the SM long-chain base (i.e., the 2NH and the 3OH) for StnII recognition. We prepared methylated SM-analogs which had reduced hydrogen bonding capability from 2NH and 3OH. Both surface plasmon resonance experiments, and isothermal titration calorimetry measurements indicated that StnII failed to bind to bilayers containing methylated SM-analogs, whereas clear binding was seen to SM-containing bilayers. StnII also failed to induce calcein release (i.e., pore formation) from vesicles made to contain methylated SM-analogs, but readily induced calcein release from SM-containing vesicles. Molecular modeling of SM docked to the phosphocholine binding site of StnII indicated that the 2NH and 3OH groups were likely to form a hydrogen bond with Tyr135. In addition, it appeared that Tyr111 and Tyr136 could donate hydrogen bonds to phosphate oxygen, thus stabilizing SM binding to the toxin. We conclude that the interfacial hydrogen bonding properties of SM, in addition to the phosphocholine head group, are crucial for high-affinity SM/StnII-interaction.

year	journal	country	edition	language
2013-05-01	Biochimica et biophysica acta

10.1016/j.bbamem.2013.01.018 https://pubmed.ncbi.nlm.nih.gov/23376330