Chromosome 22 – Myoglobin (a brief history of structural biology)


Exercise. Love it or hate it, we’ve
all got to do it. And it’s thanks to a protein
called myoglobin that we can extract oxygen from our red
blood cells and store it in our muscles. Encoded by a gene on chromosome
22, myoglobin has a key role in providing oxygen for
the biochemical reactions that keep us moving. The protein also has a very
significant place in the history of 20th century
science, and it all started with this. Here at the science museum in
London is an early model of the myoglobin molecule. And while it may not look
very impressive– indeed, the model is
rather disgusting– it represents a landmark
achievement. This, the culmination of over
20 years’ work by scientists working in Britain, is the very
first protein structure to have been seen
by humankind. The model was built in 1958 by
John Kendrew using information collected by firing
x-rays at crystals of sperm whale myoglobin. By measuring the pattern of
spots generated as the myoglobin crystals scattered the
x-rays into many different directions, he was able
to calculate the structure of the molecule. This early model is
relatively crude. It only shows the overall
shape of the protein. But that’s because Kendrew’s
first crystals weren’t very good. But the technique, x-ray
crystallography, would come to revolutionise the way that
we study biology. And since 1958, it has allowed
scientists to work out the structures of many different
biological molecules from the enzymes that digest our food,
to the ion channels that conduct electric signals
in our brains. Today in my lab, we still use
many of the same techniques that Kendrew first applied
to myoglobin. Within a few years, he had
improved his original crystals and was able to reveal the true
complexity of myoglobin’s atomic structure, unveiling its
beautiful helices and the precise arrangement of bonds
between its atoms. You can now see exactly how the
protein chain falls around the porphyrin group to create
a binding site for a single molecule of oxygen. One of the most interesting
things about this early work was that when Max Perutz applied
crystallography to study horse haemoglobin, the
molecule that transports oxygen in red blood cells, he
could see for the first time that it was very similar in
structure to myoglobin. This showed not just the
evolutionary relationship at the molecular level between
different species– horses and whales– but also that evolution could
adapt a relatively simple structure and give it a more
complex form and function. In fact, if you take a glance
to the right of Kendrew’s model at the science museum,
you’ll see Max Perutz’s structure of haemoglobin, which
is made of four chains, each of which looks very
like myoglobin. From that humble, rather hideous
start in 1958, it’s amazing how far we’ve
travelled. Over 90,000 structures of
protein, DNA, and RNA molecules have now been
determined by x-ray crystallography, giving us
detailed insights into how life operates at the
molecular level.

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