New insights into molecular machines
Researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, collaborating with Cellzome, have completed the analysis of the molecular machines in common baker's yeast (S. cerevisiae). 'If you think of the cell as a factory floor, up to now, we've known about some components of a fraction of the machines. That has seriously limited what we know about how cells work. This study gives us a nearly complete parts list of all the machines, and it goes beyond that to tell us how they populate the cell and partition tasks amongst themselves,' said Giulio Superti-Furga of Cellzome, who launched the project four years ago. The research extracted complete proteins from cells using a process called tandem affinity purification, which was developed only in 2001 by EMBL researchers. The proteins were then studied using mass spectrometry and bioinformatics to unlock the mysteries of the yeast proteins. The study uncovered 257 new molecular machines in addition to more detailed information about the machines already known. EMBL was supplied computational solutions to help gain insights into the protein complexes. One reason this had been so difficult in the past is that the molecular machines are not stable entities, but continually change by dismantling and reassembling themselves into new configurations, depending on the task. 'It would be a logistical nightmare if the cell had to build every machine from scratch any time it needed to do something. We've discovered that the reality is different. Cells use a mixed strategy of prefabricating core elements of machines and then synthesizing additional, snap-on molecules that give each machine a precise function. That provides an economic way to diversify biological processes and also to control them,' said EMBL team leader Anne-Claude Gavin. So, molecular machines may adapt to circumstance by producing specific parts for specific tasks. The modular arrangement of these building blocks has proved a major triumph for the study, as traditional techniques have not been able to look at molecules of this size in detail before - too small for microscopes, but too large for X-ray crystallography.
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