LA JOLLA, CAJune 5, 2014A team led by researchers at The Scripps Research Institute (TSRI) has used advanced electron microscopy techniques to determine the first accurate structural map of Mediator, one of the largest and most complex "molecular machines" in cells.
Mediator is crucial for the regulation of most genes' activity and works in the cells of all plants and animals. The mapping of its structurewhich includes more than two dozen unique protein subunitsrepresents a significant advance in basic cell biology and should shed light on medical conditions involving Mediator's dysfunction, from cancer to inherited developmental disorders.
The finding demonstrates how recently developed molecular imaging methods can be applied to characterize large and important protein complexes.
"Being able to determine how these large molecular machines look, how they're organized and how they move, will be critical for a better understanding of many key processes in cells," said TSRI Associate Professor Francisco J. Asturias, the senior author of the study, which was published on June 5, 2014 by the journal Cell.
A Complex Machine
The detailed map of Mediator comes nearly 20 years after the complex was first described by Stanford University biologist Roger Kornberg and colleagues. Kornberg, whose lab members at the time included Asturias, later won a Nobel Prize for his work on the gene transcription machinery of cells.
This gene transcription machinery evolved to perform one of the most basic and routine functions in biology, namely the copying of the information encoded in the DNA of genes into portable RNA "transcripts"some of which stay and work in the cell nucleus, while others exit the nucleus and are translated into proteins.
Each cell has its own pattern of gene transcription activity, determined by a regulatory system in which Mediator plays an indispensable role. The huge Mediator compl
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Scripps Research Institute