Actinoporin/Coral Papers MSC462
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This 3 page Class Notes was uploaded by Zack Bauman on Sunday February 15, 2015. The Class Notes belongs to MSC462 at University of Miami taught by Dr. Liza Merly in Fall. Since its upload, it has received 209 views. For similar materials see Marine Biomedicine in Marine Science at University of Miami.
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Date Created: 02/15/15
Molecular Mechanism of pore formation by Actinoporins Sea anemones sedentary animals that rely on toxins to capture and digest prey as well as an important defense from predation Among various toxins cytolytic proteins actinoporins are a very important component of venom which is very potent Actinoporins Action Target cell membranesform pores causing cell lysis and death Speci cmake pores only in membranes that contain sphingomyelinkind of lipid Interest Used as model proteins to study protein membrane interactions speci c recog of lipids etc o 2 most studied Equinatoxin Stycholysin II o Actinoporins not only found in sea anemones actinoporinlike proteins found in 3 animal phyla and 2 plant phyla Structural similarityB fodused for speci c binding equivalent amino acids in binding site indicate same mechanism of binding binding site located on same side of sandwich Evidence Toxin not active against bacterial spheroblasts which lack sphingomyelin in membranes Equitine didn t form pores in phospatidylcholine lipid membrane without presence of sphingomyelin Sticholysin had binding sites for phosphocholine head group of sphingomyelin Study showed toxin didn t form pores in liposomes containing sphingolipids from sea anemone only worked when sphingomyelin added to liposomes Why protein doesent act against sea anemones membranes Anemones contain large proportions of phosphonosphingolipids which have a diff phospholipid head group makes toxin act speci cally on prey membranes that contain sphingomyelin Actinoporin also make pores in phosphatidychoine membranes containing colesterol Why lnduces microdomain formationalters phosphorylcholine group making it accesible for toxin binding Hypothesis that eq recognises sphingm tested using Direct binding assays Mutagenesis Lipid dot bb assays Surface plasman resonance experiments Showed eq speci cally bind sphingomyelin or its analogue but not other lipids particularly phosphatidylcholine or colesterol Phosphatidylcholine and sphingomyelin have same phosphyl choline head group toxin needs to recognise sphingomyelin elsewhere in region below headgroup with Trp 112 and Tyr 113 side chains imp for further lipid recognition Actinoporin formation is a multistep process 1 Toxin recognized sphingomyelin using aromatic rich region and POC binding site attaches to membrane 2 Nterminal segment is transferred to lipid water interface 3 Toxin oigomerises on the surface of the membrane alpha helices 4 3 or 4 monomers insert into the membrane 5 N terminus is inserted through membrane to form ion conductive pathway pore Relates to MSC 462 Sponges Mucus vs actinoporin toxins for protection from predation Same potential use for the actinoporin for speci c cancer niches Piralt o Extraction of toxin for very speci c and powerful analgesic like Piralt Coral and its various uses Review Paper 21115 Antiin ammatory effects Arthritic counter one coral was isolated from sinularia and was found to be potent in treating adjuvantinduced arthritis o It inhibits the production of pro in ammatory proteins iNOS and Cox 2 in murine macrophages Anticancer properties Sinularian again was a new inhibitory 50 of tumor growth in cell lines 0 Down regulation effects with cytotoxins and apoptosis production Potential antiviral properties 0 Very effective on a variation herpes virus Hard tissue therapy Naturally occurring calcium in coral aragonite and calcite will assist with protecting against and reversing bone loss when used with zeolite Scientists are looking into using the bone repair method for human teeth Neuroprotection Parkinson s disease treatment 0 Associated with in ammation and apoptosis 0 11dehydrosinulariolide Blocks two in ammatory pathways iNOS and Cox 2 Neuropathic pain reducer Analgesics o Austrasulfone iNOS and Cox 2 Other coral uses Coral sand can be used as a silicon source to reduce blood pressure Hypertensive rats can be used to improve the expression of genes that increase cardiovascular health Criticism Too little information on the effects of the drugs 0 Where the drugs are in clinical trials 0 Little to no use of the graphs
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