Conformational landscape of a virus from single-particle scattering using a X-ray Free Electron Laser*

Using a manifold-based analysis of experimental diffraction snapshots from an X-ray free electron laser, we determine the three-dimensional structure and continuous conformational landscape of the PR772 virus. Our results indicate that a single conformational coordinate controls reorganization of the genome, growth of a tubular structure from a portal vertex and release of the genome[1]. We have shown that XFEL-based single-particle imaging, when combined with novel data analytical approaches, has the potential to reveal important conformational changes in biological entities, identify the conformational coordinates controlling key processes, and map the conformational landscapes associated with individual or multiple conformational coordinates. The emerging capability of XFELs to generate very large data sets promises unprecedented access to rarely occupied rate-limiting conformations, which control the course of important biological processes. These results demonstrate that single-particle X-ray scattering has the potential to shed light on key biological processes.

[1] Hosseinizadeh, A. et al. Conformational landscape of a virus by single-particle X-ray scattering. Nat. Methods (2017). doi:10.1038/nmeth.4395