Proteins are the building blocks of
our cells. Understanding their shape and
how they fit together could help us
treat pain and even cure diseases.
Scientists have been trying to get a
good look at some proteins, but for years,
the best we could see was a blurry blob.
Many proteins are thousands of times
smaller than the width of a human hair.
Traditionally scientists used a technique
called x-ray crystallography to take
pictures of the tiny proteins. For the
x-ray imaging to work, it requires
proteins are packed together into a
stable, organized crystal. X-rays pass
through the sample to create an image.
But some of the body's most important
proteins are too floppy or wiggly to
line up into a crystal. Scientists at
UCSF have developed a better way to view these elusive proteins.
If you have a floppy molecule at all,
they just become more and more
challenging to crystallize. Really the
problem was that these are big,
complicated systems, and coming up with
new ways of studying them required
thinking about electron microscopy.
The reason cryo-EM works is that we keep the protein
in a very thin layer of liquid and we will freeze them.
This technique is called cryo-electron
microscopy. An electron gun shoots
electrons at the speed of light, passing
through the sample. Then a specially
designed high-tech camera captures the
electrons to form an image.
The camera not only improves the imaging condition and gives you a much better, sharp image,
it can record a movie instead of steady
picture.
If you had a still picture, and I was doing this with my hand during the picture, I'd have a blurry hand picture.
But with a movie, you could actually see some different steps.
A computer algorithm sorts the images and finds pictures of the protein in the same orientation.
Then software builds a composite - an accurate, high-resolution,
three-dimensional image of the protein.
And we're using the computational method to average many hundreds of thousands
molecules, or tens of thousands of them
together
to generate those three-dimensional
structures.
A structure like this one. Yifan calls it the wasabi receptor because it detects the pungent zing
in wasabi and onions, and it's part of how the body registers pain.
Scientists have known about this protein
for years but now we can finally see its
shape in 3D. That means we can begin to
build better drugs to block pain.
