OxTalks will soon move to the new Halo platform and will become 'Oxford Events.' There will be a need for an OxTalks freeze. This was previously planned for Friday 14th November – a new date will be shared as soon as it is available (full details will be available on the Staff Gateway).
In the meantime, the OxTalks site will remain active and events will continue to be published.
If staff have any questions about the Oxford Events launch, please contact halo@digital.ox.ac.uk
Electron microscopy (cryo-EM) is an essential tool to visualize proteins in near-native conditions. This is particularly true when dealing with heterogeneity—a hallmark of biological systems in health and disease. I will discuss how cryo-EM can uncover clinically relevant structural states using the membrane channel Pannexin-1 (PANX1) as a case study. PANX1 plays key roles in inflammation, ischemic injury, and immune cell activation due to its central role in ATP release. Yet, its regulation of the ATP-release state remains poorly understood. Using cryo-EM, we separated two PANX1 conformations and identified how phosphorylation stabilizes the open, large-pore state, enabling the passage of ATP and metabolites. This provides a structural basis for PANX1 activation in inflammatory and disease contexts. In a second example, cryo-EM allowed us to resolve compositional heterogeneity in a mixed protein sample, identifying three distinct structures—including one previously uncharacterized complex—at better than 3.5 Å. Together, these studies highlight cryo-EM’s power in deciphering biologically and clinically important complexity.