Entering edit mode
10.6 years ago
pavel.tyutyaev
▴
10
Dear friends,
I would like to propose an alternative route (alternative pore) through the structure of (some) an ion channel protein. The 3D-structure of the protein is already known. Which algorithm should I use (minimal energy, shortes trace?...)? Which programs do already exist for automated detection of cavities in 3D-models of proteins?
Please give me some suggestions ;)
Regards, Paul
Firstly, could you at least spell check your post? If you can't take the time to do that, why should we take the time to answer? Secondly, have you read the 2002 paper from Rod MacKinnon's lab on the structure of the ClC channel? That's the only one that comes to mind where the location and structure of the pore wasn't established fully beforehand. That would seem to be the starting point for thinking about your project.
Fixed, more or less. I just found this was an interesting question even if a bit vague.
Thanks. I spent a long time working on ion channel biophysics, so I have my own personal biases :D For what it's worth, these channels are generally crystallized with either the native ion or a large blocker in them, which makes finding the pore rather easy. Of course, this assumes that the pore exists in whatever state in which the channel is crystallized (I'm reminded of the papers describing the omega current, where knowing how S4 moved was required to really show how the pore functioned)...
Not all channels are already crystallized (less 0.1% of all) and of course not all toxins and ligands bind to the alfa-pore. But I have an other problem. I´m seeking an alternative pore in the channel with a point mutation (opens gateway) that enables this new way.
Sigh, "alpha", I won't bother with this post if you can't even get the nomenclature correct.
Today we have 2 types of pore in the same channel and I´m looking for a third one.
Do you have evidence for that this prediction would make biological sense, have you ever seen an "alternative pore" discovered elsewhere?
Thank you very much for ansver. Course, please check the papers "sigma pore in Kv1.3". J Biol Chem. 2011 Jun 3;286(22):20031-42. doi: 10.1074/jbc.M110.185405. Epub 2011 Apr 15. A novel current pathway parallel to the central pore in a mutant voltage-gated potassium channel. Prütting S, Grissmer S.