Overcoming sample limitations to enable time-resolved characterisation of a wider range of protein dynamics

Here we propose method development at the time-resolved X-ray solution scattering (TR-XSS) beamline ID09 to enable characterization of a wider range of protein targets. Our previous studies have provided critical insights into structural intermediates of eukaryotic calcium transporter SERCA1a, cooperative protein dynamics in adenylate kinase, and the rate-limiting step in bacterial calcium transport. However, the need for large sample volumes in pump-based delivery systems have limited the target proteins and also caged compounds. To overcome these limitations, we propose the use of a fixed-target microchamber chip, which will dramatically reduce demands on both the protein and caged compound. Successful implementation will enable the study of challenging protein targets such as human G-protein coupled receptors (GPCRs) and ligand-gated ion channels (LGICs), which are critical to human physiology and disease intervention.