12 June 2023 ESRFnews

Since the 1950s, almost all structural biology has involved molecules in static. Now, serial crystallography is making movies out of them and ID29 is bringing the technique to the masses.

Lights, camera, action

LIFE does not stay still. Cells divide, hearts beat, people move. The same is true at a molecular level: the proteins making up all organisms constantly fluctuate between different conformations in order to perform their essential tasks. And yet, for the most part, structural biologists only ever see biological molecules when they are lifeless, frozen in time.

That is changing. Over the past decade, scientists at the ESRF and elsewhere have been honing a new technique that illuminates molecules in motion. Serial crystallography (MX), as it is known, was first conceived for X-ray free-electron lasers (XFELs), but has since been developed at synchrotrons. Now, one of the world s first synchrotron beamlines wholly dedicated to serial MX, the ESRF s ID29, has opened to users. The beamline promises to make serial MX a routine option while maximising its potential with the EBS.

With the advent of time-resolved serial MX, we have the potential to revolutionise our understanding of life, says José Manuel Martín García, a structural biologist and ESRF user at the Institute of Physical Chemistry Blas Cabrera (IQF-CSIC) in Madrid, Spain. Understanding how protein molecules move in real time, at atomic resolution, during a biochemical reaction will allow us to develop more effective drugs and antibiotics.

Traditional MX involves growing a large molecular crystal of interest, cooling it to very low temperatures, and then exposing it to a focused X-ray beam in order to collect sufficient diffraction data hopefully before the radiation destroys it. By contrast, serial MX does not need a large crystal. Instead, it involves feeding thousands of small crystals of the same molecule through an X-ray