ligand-gated ion channels

Dr Engelbert Buxbaum engelbert_buxbaum at hotmail.com
Tue Nov 4 00:32:04 EST 2003


chrissy wrote:

> Hi!  I hope you'll allow what might be a simple question to some of
> you, but I haven't been able to find answers elsewhere.
> 
> With a multisubunit ion channel, where the subunits have multiple
> transmembrane helices, how do you tell which of a subunit's helices is
> the porelining helix?  And what are the features that predict
> cation/anion selectivity?  Does this have something to do with the
> amino acid sequence or is it more complex?
> I just finished an introductory lecture series on it, but the lecturer
> wasn't very clear.  She used the acetylcholine receptor as an example,
> and said something about a 9' leucine, but I can't find an explanation
> of that term anyway.  And how does that relate to ligand-gated
> channels in general?

Our knowledge on this topic is still rather limited. However, physical
chemistry tells us that the channel must be lined with polar and ionised
amino acids, to allow interaction with substrate. Positive ions would
require negatively charged amino acids and vice versa. So the helices
making up the channel must be amphipatic, that is, a helical wheel plot
of its sequence must show a charged and a lipophilic side. 

But in the end only high resolution 3D-structures will provide the full
answer.



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