Using a unique facility in the US, researchers at the University of Gothenburg have found a more effective way of imaging proteins. The next step is to film how proteins work—at the molecular level. |
Mapping
the structure of proteins and the work they do in cells could be the
key to cures for everything from cancer to malaria. Last year Richard
Neutze, professor of biochemistry at the University of Gothenburg, and
his research group were among the first in the world to image proteins
using very short and intensive X-ray pulses.
In a new study published in Nature Methods, the method has been tested on a new type of protein, with good results.
“To
put it simply, we’ve developed a new method of creating incredibly
small protein crystals,” says Linda Johansson, doctoral student at the
Department of Chemistry and Molecular Biology and lead author of the
article. “We’ve also shown that it’s possible to use very small crystals
to determine a membrane protein structure.”
Could become standard
There
are two major challenges when it comes to imaging proteins: the first
is to create the right sized protein crystals, and the second is to
irradiate them in such a way that they do not disintegrate. Although
Sweden has a facility for synchrotron-generated X-ray radiation—Maxlab
in Lund—this type of technology is not sufficiently light-intensive and
therefore requires large protein crystals which take several years to
produce.
Richard
Neutze was one of the researchers to float the idea that it might be
possible to image small protein samples using free-electron lasers which
emit intensive X-ray radiation in extremely short pulses—shorter than
the time it takes light to travel the width of a human hair. This kind
of facility has been available in California since 2009, and it is this
facility that was used for the study.
“Producing
small protein crystals is easier and takes less time, so this method is
much faster,” says Linda Johansson. “We hope that it’ll become the
standard over the next few years. X-ray free-electron laser facilities
are currently under construction in Switzerland, Japan and Germany.”
365,000 images
Carried
out by researchers from Sweden, Germany and the US, the study
investigated a membrane protein from a type of bacterium that lives off
sunlight. It is important to investigate membrane proteins as they
transport substances through the cell membrane and thus take care of
communication with the cell’s surroundings and other cells.
“We’ve
managed to create a model of how this protein looks,” she says. “The
next step is to make films where we can look at the various functions of
the protein, for example how it moves during photosynthesis.”
A
key discovery was that far fewer images are needed to map the protein
than previously believed. Using a free-electron laser it is possible to
produce around 60 images a second, which meant that the team had over
365,000 images at its disposal. However, just 265 images were needed to
create a three-dimensional model of the protein.
Lipidic phase membrane protein serial femtosecond crystallography
