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Fig. 1
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Our body's cells have membranes, and "ion
channels" are embedded in them. Ion channels are special proteins
which let only certain ions through the membrane. The channels build
an electro-chemical gradient, allowing nerve and heart muscle cell
signals to pass. The nerve or heart muscle cell is excited, and the
ion channel structure changes, developing pores which let the ions
through. Different channels are open to different specific ions; for
example, potassium channels only allow potassium ions through.
Poisonous animals use very specific toxins to target channels; the
toxins block the channels and make it impossible for electric signals
to move through the membrane - often killing the cell.
These kind of interactions had not been well investigated at a
structural level - even though scientists had made great strides
studying ion channels, using x-ray crystallography. Scientists from
the Max Planck Institute for Biophysical Chemistry in Göttingen,
working together with researchers from the Institute for Neural Signal
Processing in Hamburg and French colleagues from the University of
Marseille, combined a new method of solid-state NMR with particular
protein synthesis procedures and looked at the example of poison from
the north African scorpion Androctonus mauretanicus mauretanicus, to
determine how bacterial potassium channels interact with toxins at an
atomic level.
Fig.2: The
toxin-ion channel complex's structure. Scientists used solid-state NMR
to discover how kaliotoxin - poison from a north African scorpion (see:
Fig. 2) - affects a bacterial potassium channel. They looked at NMR
data from samples of the channel before and after a toxin-ion channel
complex is created (above, red and green). From this they developed a
structural model of the binding pocket (below). The binding changes
the toxin's structure (red). Areas marked blue are unaffected.
Image © Max Planck
Institute for Biophysical Chemistry
The researchers first examined the
electrophysiological characteristics of the "poisoned" channel protein.
The scientists "spin-marked" some of them and investigated them with
solid-state NMR. Spin-marked proteins contain carbon and nitrogen
atoms with an intrinsic magentic moment (spin) which strengthens the
NMR's signals. Looking at spectroscopic data before and after the
toxin affected the channel, it turned out that the poison attaches to
a particular area of the channel - the pore region - and changes the
area's structure. The poison is thus only effective when it recognises
a particular amino acid sequence in the ion channel. It is also
important how intrinsically flexible the binding partner is; for a
strong interaction to take place, the molecules of both partners have
to be able to change their structures.
Applying these new spectroscopic
methods, scientists are now better understanding the pharmacology and
physiology of potassium channels. This could lead to better, more
specific medications. [EC] |
