Abstract

Biomolecules are highly dynamic, however most structures determined so far only provide a static picture of the molecule. Serial Femtosecond Crystallography (SFX) provides a novel concept for structure determination, where X-ray diffraction “snapshots” are collected from a fully hydrated stream of nanocrystals, using femtosecond pulses from high energy X-ray free-electron lasers (XFELs). The XFEL pulses are so strong that they destroy any solid material. However, a femtosecond is extremely short (1 fs = 10-15 s). To illustrate this time domain just consider that the time difference between a fs and a second is the same as between a second and 32 million years. With these ultrashort pulses X-ray damage is “outrun” and structural information (i.e. diffraction) from the crystals is observed before destruction takes effect [1]. The first proof of concept of serial femtosecond crystallography was achieved using Photosystem I, a larger membrane protein complex involved in Photosynthesis as a model system [2, 3]. The structure of non-damaged biomolecules can now be determined, unravelling their function at the atomic scale [4, 5] that include important human membrane-bound receptors that are key players in vision (rhodopsin-arrestin) [6], hormone function (serotonin receptor) [7], control of blood pressure (Angiotensin receptor) [8], development of cancer (smoothened receptor) [9] as well as receptors that may provide new avenues against drug abuse (opioid receptor) [10].

Authors and Affiliations