Chemistry Reference
In-Depth Information
FIGURE 9.2
Na
þ
- and K
þ
-selective binding sites in transport proteins. (a) Two Na
þ
binding sites in the LeuT Na
þ
-dependent pump
(PDB code 2A65). (b) Four K
þ
binding sites in the KcsA K
þ
channel (PDB code 1K4C).
(From
Gouaux &MacKinnon, 2005
.
Reproduced with
permission from John Wiley & Sons.)
partial-charge-bearing oxygen atoms. The size of the cavity formed by the selectivity filter sites is a good match
to the K
þ
ion, with a mean K
þ
e
O distance of 2.84
˚
. The greater number of oxygen atoms forming the K
þ
-
binding sites (eight oxygen atoms) compared to that of the Na
þ
sites (five or six oxygen atoms) is a simple
geometric consequence of the larger radius of K
þ
, which allows a greater number of oxygen atoms to surround
the ion.
What the comparison of LeuT and the K
þ
channel tells us about alkali metal ion selectivity in transport
proteins is the following. The Na
þ
and K
þ
sites both contain oxygen atoms, mostly the kind with partial negative
charges. This agrees well with the rules learned from host/guest chemistry with ions. There is a tendency for Na
þ
sites to contain one formal charge, attributable to the smaller radius and higher charge density of the Na
þ
ion,
although a formal charge is not essential. What appears as the most important factor distinguishing Na
þ
and K
þ
sites is the size of the cavity formed by the binding site. This suggests that the essence of alkali metal cation
selectivity is similar to that in ion binding by small molecules: The protein selects for a particular ion, Na
þ
or K
þ
,
by providing an oxygen-lined-binding site of the appropriate cavity size.
POTASSIUM CHANNELS
K
þ
channels selectively transport K
þ
across membranes, hyperpolarise cells, set membrane potentials, and control
the duration of action potentials, among a myriad of other functions. They use diverse forms of gating, but they all
have very similar ion permeabilities. All K
þ
channels show a selectivity sequence of K
þ
w
Rb
þ
>
Cs
þ
, whereas
the transport of the smallest alkali metal ions Na
þ
and Li
þ
is very slow
typically the permeability for K
þ
is at
least 10
4
that of Na
þ
. The determination of the X-ray structure of the K
þ
ion channel has allowed us to understand
how it selectively filters completely dehydrated K
þ
ions, but not the smaller Na
þ
ions. Not only does this
molecular filter select the ions to be transported, but also the electrostatic repulsion between K
þ
ions, which pass
through this molecular filter in Indian file, provides the force to drive the K
þ
ions rapidly through the channel at
a rate of 10
7
e
The first voltage-gated potassium channel to be identified was the gene encoding the Shaker mutation
3
in
the fruit fly Drosophila.
Figure 9.3
presents the first pictures of the tetrameric Shaker K
þ
channel with
e
2. The 2003 Nobel prize for chemistry was awarded to Rod MacKinnon for his pioneering work in this area.
3. These mutant fruit flies shake violently when anaesthetised with ether.
