Genome-wide analysis of intractable proteins

A procedure has been devised for obtaining structures, potentially across entire genomes, of proteins that are intractable to crystallographic analysis (Proc. Natl. Acad. Sci. USA, published online May 11, dx.doi.org/10.1073/pnas.0602606103). In the technique, developed by Michael Strong, David Eisenberg, and coworkers at UCLA, computational genomic analysis is used to identify a protein likely to interact functionally with an intractable protein. The two partners are then coexpressed as a complex in bacteria, crystallized, and structurally analyzed. The idea is that complexes may be more easily expressed and more readily crystallized than their individual component proteins. The researchers demonstrated the technique by analyzing a complex (shown) of the proteins PE (red) and PPE (blue) from tuberculosis bacteria. "The predicted complex was readily expressed, purified, and crystallized, although we had previously failed in expressing individual PE and PPE proteins on their own," the researchers note. "Our entire procedure for the identification, characterization, and structural determination of protein complexes can be scaled to a genome-wide level."