While cryo-electron microscopy (cryo-EM) is rapidly gaining in popularity, its time resolution is currently insufficient to directly observe proteins in action, leaving our understanding of these nanoscale machines fundamentally incomplete. We have recently introduced a novel approach to time-resolved cryo-EM that affords microsecond time resolution and thus promises to overcome these...
Fourth generation synchrotron sources create new opportunities for expanding the research in structural biology and in protein crystallography in particular. The ESRF Extremely Brilliant Source upgrade programme was completed with the construction of the new ID29, the first world beamline completely dedicated to room temperature experiment and time-resolved macromolecular serial...
A frontier challenge in bioscience is to obtain deep mechanistic understanding from atomic resolution, time-resolved structures of macromolecules engaged in function. To this end, we have developed sample-efficient delivery and reaction initiation strategies that use room temperature microcrystal slurries and serial crystallography methods for time-resolved studies. Our overriding hypothesis...
Mammalian rhodopsin is our light receptor for vision. It belongs to the highly druggable G protein-coupled receptor family. It hosts the retinal chromophore which, like a switch, isomerizes in less than 200 femtoseconds upon photon absorption. This triggers sequential intramolecular changes in rhodopsin, initiating the signalling cascade generating in milliseconds vision events to the brain...
Single molecule scattering experiments with femtosecond high-intensity free-electron laser (XFEL) pulses provide a new route to macromolecular structure determination. In these serial crystallography experiments, and despite the ultra-high brilliance of XFEL lasers, the signal to noise is expected to be in the extreme Poisson regime with only 10-100 recorded diffracting photons per image....
The sarcomere is the smallest contractile unit in cardiac and skeletal muscle, where actin and myosin filaments slide past each other to generate tension. This molecular machinery is supported by a subset of highly organised cytoskeletal proteins that perform architectural, mechanical, and signalling functions. Sarcomere ultrastructure is highly organised and delimited by Z-disks, which play a...
