[Myotox] Manuscript?

[Borries Demeler]

Dear Colleagues,
it's been quiet on this list, and I am wondering if we reached a state where we want to publish the results we have collected so far for the mytoxin-II story. Allow me to provide a brief summary of our observations:

1. By AUC, MT-II remains monomeric in PBS up to very high concentrations (I believe 20 mg/ml was the highest we studied),
2. At high [SDS] (>CMC), we observed a structure that could be a dimer. This is replicated in SDS-PAGE and in X-ray crystallography
3. In AUC, we observed formation of a discrete hexamer or heptamer of MT-II in the presence of very low SDS.
4. Increasing [SDS] would result in higher order aggregates/oligomers than hexamer, but s-value distributions were not discrete and quite heterogeneous, and finally dissociate into apparent dimer species.
5. The same effect could not be reproduced with other lipids or detergents
6. NMR shows an unusually strong interaction between MT-II and SDS at lower SDS concentrations. The alpha methylene exhibits high stress similar to that seen in an epoxy ring. Ar first sight it appears to be an AB quartet. Simulations show that the 2JHH of the methylene is very small indicating strain.
7. electrophysiology experiments with bilayer membranes did not produce results - Sebastien, are there any updates?
8. negative staining and cryoEM turned out to be a dead end
9. MD simulations involving SDS by Francisco suggest a dimer formation 

I would like to know what, if any, experiments should be performed before we decide to publish? I propose to write up what we have so far and send it to Eur. Biophysical Journal. We are editing a special issue to celebrate the 25th AUC conference anniversary, held this past July in Lethbridge. If you are interested in contributing to this article, please indicate what data/methods you would like to contribute. Since the major discovery here is based on AUC (hexamer formation), I would propose that we submit this as an AUC focused manuscript.

I'm open to any and all suggestions and would like to get your feedback.

I'm also attaching a summary of what we have from Francisco and from our lab.

Looking forward to get your feedback.

Regards, -Borries
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