The work of two postdocs in different labs at the University of Washington in Seattle has solved the mechanics of a protein complex involved in DNA repair, replication and transcription (see page 590).

Ti Li, a fellow in Ning Zheng's lab, took on the structure of the ubiquitin-ligase machinery. “This has many parts, and some are very difficult to prepare from bacteria,” says Zheng. Li separately purified three components of the complex, two from Escherichia coli and one from insects, then put them together. This was daunting; she could only obtain minute amouts of the sample and had no clear guidelines on when and how to attach the components.

Li then took advantage of a viral protein that hijacks the cellular protein machinery to obtain diffracting crystals.

Next, Zheng's group sought insight into how the complex works in cells. The team drew on a method developed by Stephane Angers of Randall Moon's lab. He had developed a proteomics method to study the WNT pathway, a key player in development and cancer.

Angers found that some WNT-pathway proteins are controlled by ubiquitin-ligase machinery similar to that which Li had studied. “We realized how powerful his method was and how it could be applied to this system,” says Zheng. The method effectively identified a number of novel proteins.