The honour of solving the first new protein structure on the PX2 (protein microcrystal beamline) has been claimed by a team from the Walter and Eliza Hall Institute of Medical Research.

In March 2009, Marc Kvansakul and his colleagues used the PX2 beamline to solve the structure of a particularly challenging viral protein-peptide complex. The team already knew the structure of the vaccinia virus F1L protein on its own, but they wanted to determine the structure of the protein interacting with one of the mammalian peptides it binds to so they could see how it might be possible to block the protein's action. In 2008, they produced crystals of the protein-peptide complex, but its structure proved elusive.

The structure was finally solved on the PX2 beamline in less than half an hour.

"The new beamline has definitely proved its worth when dealing with our crystals," Marc said. "Despite a number of attempts using the PX1 beamline, we were never able to successfully solve the structure from diffraction data obtained from these poorly-diffracting crystals.

"However, the combination of a very finely focused and highly intense beam, allowing us to pick a well-ordered region of our crystal, together with improved detector quality that minimised data overlap, enabled us to make the leap in diffraction data quality that finally delivered the structure."

Beamline scientist Tom Caradoc-Davies said the PX2 beamline was specifically designed for microcrystals and weakly-diffracting crystals. Its microfocus beam also caters for crystals such as the WEHI team's protein-peptide complex where the unit cell (the main repeating unit of a crystal structure) has one very long edge; this would otherwise create a diffraction pattern with overlapping spots almost impossible to resolve.

The F1L protein enables the vaccinia virus to hijack a crucial defence mechanism in the cells it invades, essentially preventing the cells from committing suicide and ensuring it can continue to reproduce more viral particles.

The WEHI project is part of an ongoing investigation under the overall direction of Peter Colman. The group is studying mammalian and viral proteins to learn more about the fundamental mechanisms of cell apoptosis - also referred to as programmed cell death or cell 'suicide switches'.

In 2007, Marc Kvansakul was part of a team that solved the first new protein structure on the PX1 (high-throughput protein crystallography) beamline at the Australian Synchrotron. The work showed in atomic detail how the BHRF1 protein from the Epstein-Barr virus intercepts the death cue that prevents an infected cell from undergoing programmed cell death.


L to R: Alex Caputo, Oliver Clarke, Marc Kvansakul and Tom Caradoc-Davies discuss the first protein structure solved on the protein micro-crystal (PX2) beamline.

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