"Science" lists first protein structure from an X-ray laser among top ten achievements in 2012

The high profile scientific journal "Science" has chosen the first new biological structure solved by an X-ray free-electron laser as one of the ten most important scientific breakthroughs in 2012. "The advance demonstrates the potential of X-ray lasers to decipher proteins that conventional X-ray sources cannot", the journal states in a press release issued on Thursday. Last month, a team of scientists from Germany and the U.S. had revealed the structure of the inactive form of an enzyme that is key for the survival of the single-celled parasite Trypanosoma brucei that causes African sleeping sickness (press release).

A map of intensities merged using the CrystFEL software suite from almost two hundred thousand diffraction patterns obtained from in vivo grown crystals of Trypanosoma brucei cathepsin B. This map is used to synthesize the three-dimensional molecular structure of the enzyme. Image courtesy of Karol Nass, CFEL.

"This is the first new biological structure solved with a free-electron laser," said DESY scientist Prof. Henry Chapman from the Center of Free-Electron Laser Science (CFEL), who led the international team together with Prof. Christian Betzel from the University of Hamburg and Dr. Lars Redecke from the joint Junior Research Group "Structural Infection Biology using new Radiation Sources (SIAS)" of the Universities of Hamburg and Lübeck. The group had used the world's most powerful X-ray laser, the Linac Coherent Light Source (LCLS) at the U.S. National Accelerator Laboratory SLAC, to investigate tiny microcrystals of the enzyme.

X-ray free-electron lasers (XFELs) are relatively new scientific tools. DESY is the main shareholder of the European XFEL currently under construction in Hamburg. Shining about a billion times brighter than any other X-ray source, XFELs have pushed the concept of X-ray crystallography beyond its previously understood limits. "While the full potential of free-electron lasers has yet to be explored, we're already beginning to see their merits," explained Chapman. "Avoiding radiation damage, working at room temperature, and only needing microscopic crystals will have a huge impact on structural biology."

“Performing one of the first biological experiments using the new X-ray radiation source and sophisticated sample injection and data analysis techniques was a challenging and demanding task for everyone in the team," said Karol Nass, PhD student supervised by Chapman and one of the first authors of the article. "However, with time this technology has a big chance to evolve into a user friendly technique.”

The current limitations of the new technique are due to the inefficient consumption of sample - most of the crystals currently remain unused - and limited beamtime. "These are both engineering issues that can be solved, and the 27,000 pulses per second at the European XFEL will go a long way in addressing both these concerns," said Chapman. "In the long run I think that we will see dedicated facilities for structural studies." This will enable science to carry out detailed studies of the dynamics of proteins and their interactions.

“Particularly the combination of the free-electron laser technique with the other innovation of protein crystallisation within cells will provide a compelling path to obtain protein structures, if we could understand the mechanism of in vivo crystallisation in more detail in the future,” said Redecke, the other first author of the study. “This will open the door to look at proteins, which could not be traced by conventional crystallography so far, for example membrane proteins, which are of particular interest as drug targets”, concluded Betzel.

As the "breakthrough of the year" in its annual list, the journal "Science" chose the discovery of a Higgs-like boson at the Large Hadron Collider (LHC), in which DESY scientists also played a substantial part.