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Studying the Structure of Molecular Machines: Two New Initiatives

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About a dozen US researchers met at the Scripps Research Institute at the end of last month to discuss a national effort for determining the structure of cellular protein complexes. The idea is to bring together mass spectrometry, electron microscopy, and x-ray crystallography in a large-scale consortium similar to the Structural Genomics Initiative of the NIGMS, according to Steve Almo, an x-ray crystallographer from Albert Einstein College of Medicine, who led the meeting together with electron microscopist Ron Milligan of Scripps.

The end product would be a database of low- and high-resolution structures of protein complexes, and the project could lead to a novel approach for discovering drug targets that aims to break up functional protein “machines,” Almo said.

The impetus for the proposal, he said, was a publication in Nature last January in which researchers from Cellzome and EMBL analyzed 232 multiprotein complexes in yeast by mass spectrometry. In addition to yeast, the proposed consortium may initially study protein complexes from Dictyostelium and bacteria, and later add mammalian cells, he said.

Almo and Milligan are currently preparing a short outline of the project, which they plan to use to brief funding agencies by the end of this month. Syrrx and Cellzome have also expressed interest in joining forces with the consortium, Almo said. According to Nature, Cellzome is also leading a similar European initiative to study the structure of protein complexes.

— JK

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