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8 | advancing Knowledge
Opening up
Structural studies have provided new insights
into bacterial ion channel opening.
Attention
seeking
Attention is in short supply – but can
be used more flexibly than once
thought.
1
Ion channels allow cells to transport
material across their membranes
selectively. How opening and closing
is achieved, however, is poorly
understood. Two recent studies have
shed light on the dynamics of two
important bacterial channels – a
pressure-sensitive channel and a
drug efflux pump.
The MscS channel enables bacteria to
survive a sudden osmotic shock. Faced
with low osmotic pressure outside, a cell
would explode were it not for the opening
of pressure-sensitive channels, which
allow ions and small solutes to escape,
thus relieving pressure.
The ion channel consists of seven MscS
molecules arranged in a barrel shape,
but its structure is known only in a closed
state. Now, James Naismith in St Andrews,
Ian Booth in Aberdeen and colleagues
have used a combination of structural
modelling and electrophysiological
analysis of engineered channels to work
out the structure of the open state and
the mechanism of channel opening.
According to their model, the seven MscS
monomers tilt and slide to open and close
the channel – much as the diaphragm
mechanism controls the iris aperture in a
camera.
A similar approach has been adopted by
Wellcome Trust Senior Research Fellow
Ben Luisi in Cambridge. His group’s focus
has been a drug efflux pump, which ejects
drugs from the cell. The pump consists of
an inner membrane channel (AcrB), an
outer membrane channel (TolC) and a
protein linking the two (AcrA).
TolC is present as a trimer, part of which
forms a plug that meshes with the linking
component, AcrB. When particular
residues in this area were altered, the
pump remained partially open, and its
structure suggested a mechanism for
docking with AcrB.
Opening and closing seems to depend
on an initial interaction between TolC and
AcrB, which squeezes open the TolC
channel slightly and exposes grooves for
binding of the third component, AcrA.
Once engaged, AcrA docks into TolC,
fully opening the channel.
With ion channels playing so many critical
biological roles, understanding how their
opening and closing is controlled is an
important challenge – not least by
suggesting routes toward the
development of targeted therapeutics.
Wang W et al. The structure of an open form of an
E. coli mechanosensitive channel at 3.45 Å resolution.
Science 2008;321(5893):1179–83.
Bavro VN et al. Assembly and channel opening in a
bacterial drug efflux machine. Mol Cell 2008;30(1):
114–21.
This research was supported by the Wellcome
Trust and other funders.
Faced with a barrage of visual
information, our brains concentrate on
– or attend to – limited aspects of a
scene. According to conventional
thinking, only four or five objects can
be attended to at a time. Rather than it
being a simple numerical capacity,
however, Paul Bays and Masud
Husain at University College London
(UCL) have found that people have a
limited supply of attention, which is
parcelled out among different parts of
a scene. Meanwhile, Alex Thiele and
colleagues in Newcastle have found
further evidence that the cellular
mechanisms of attention depend on
the neurotransmitter acetylcholine.
Attending to parts of a scene places
demands on short-term or ‘working’
memory. To test the capacity of working
memory, the UCL team briefly showed
subjects a screen featuring coloured
shapes before changing the position of
one of the shapes. As the number of
shapes increased, subjects were less
able to spot changes. But no sudden
change occurred at four or five objects.
So working memory seems to have a
small capacity, but instead of being limited
to a fixed number of items, it can be spread
out over a small but variable number.
Remarkably, when subjects’ eye
movements were tracked while they
were looking at shapes in a specified
Images
1 Open and closed states of the MscS ion channel.
2 Attention depends on the action of acetylcholine-containing
neurons in the brain.
3 Lung cancer cells.