Yeast Cells Brim With Machinery

It's challenging enough to elucidate the structure and function of a single protein in a cell, yet proteomics researchers are wielding a bevy of high-throughput analytic tools and computational methods that provide group snapshots of the thousands of proteins that simultaneously carry out life's activities.

A team of 32 academic and industry scientists in Germany has now shown how 2,760 proteins in budding yeast cells assemble into 491 complexes, 257 of which had not been identified before (Nature, published online Jan. 22, dx.doi.org/10.1038/nature04532).

"It's a bit like human society," suggests Gitte Neubauer, one of the researchers from a Heidelberg subsidiary of the drug discovery company Cellzome. "People come together in different groupings to fill particular functions," she says. For their vast survey of yeast proteins, Neubauer and her Cellzome colleagues teamed with researchers at the Heidelberg unit of the European Molecular Biology Laboratory.

The researchers were able to extract, purify, and identify 2,760 distinct proteins using a method known as TAP-MS, short for tandem affinity purification-mass spectrometry. The method allows each of the nearly 6,500 genes of Saccharomyces cerevisiae cells to be modified so that their associated proteins bear hooks for specialized antibodies used in the extraction and purification process.

Further analysis of the data indicated how the proteins join into complexes that can perform cellular jobs such as generating energy and defense. These complexes are made up of "cores" involving up to 23 proteins, smaller "modules" of a few proteins, and individual proteins that all mix and match into the cell's machinery. Even with this sizable inventory of protein complexes, the researchers suspect that the study still missed as many as 300 cores.

"If we are going to understand how a cell works, we need to understand the protein complexes within them," says Anuj Kumar, a functional genomics researcher at the University of Michigan. "This is a huge step toward that goal."