Exciton coupled circular dichroic studies of self-assembled brevetoxin-porphyrin conjugates in lipid bilayers and polar solvents.
BACKGROUND
Brevetoxins, involved in the 'red tide' as well as shellfish poisoning, are known to bind to cell membranes and membrane proteins. Brevetoxin B (BTX-B) interacts specifically with neuronal sodium channels. We recently found that BTX also induces selective ion movements across lipid bilayers through transmembrane BTX self-assemblies.


RESULTS
We examined the self-assembly of several BTX derivatives in the presence and absence of cations and lipid bilayers using the powerful porphyrin chromophores as circular dichroism labels. BTX derivatives self-assemble into tubes, which can bind to metals both when soluble and when inserted into the bilayer to form transmembrane pores. Depending on the tendency of the BTX derivative to self-aggregate (the critical 'micelle' concentration, cmc), it may aggregate in solution before membrane insertion, or may insert itself into the membrane as a monomer before assembling the pore.


CONCLUSIONS
The active BTX-B complex in lipid bilayers is a cyclic, transmembrane self-assembly consisting of antiparallel aligned BTX molecules that can mediate selective ion movement through membranes. The differences in pore formation mechanisms between BTX derivatives may be reflected in differences in pore formation by natural BTX variants, perhaps explaining their varying levels of toxicity.
Matile
S
S
Department of Chemistry, Columbia University, New York, NY 10027, USA. kn5@columbia.edu
Berova
N
N
Nakanishi
K
K
D002942:Circular Dichroism; D007476:Ionophores / Q000737:chemistry; D008051:Lipid Bilayers; D008387:Marine Toxins / Q000737:chemistry*; D035964:Oxocins; D011166:Porphyrins / Q000737:chemistry*; D012997:Solvents; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D000095702:Polyether Toxins
D007476:Ionophores; D008051:Lipid Bilayers; D008387:Marine Toxins; D035964:Oxocins; D011166:Porphyrins; D012997:Solvents; C053342:brevetoxin; D000095702:Polyether Toxins