Navigation Links
The closest look ever at the cell's machines

Today researchers in Germany announce they have finished the first complete analysis of the "molecular machines" in one of biology's most important model organisms: S. cerevisiae (baker's yeast). The study from the biotechnology company Cellzome, in collaboration with the European Molecular Biology Laboratory (EMBL), appears in this week's online edition of Nature.

"To carry out their tasks, most proteins work in dynamic complexes that may contain dozens of molecules," says Giulio Superti-Furga, who launched the large-scale project at Cellzome four years ago. "If you think of the cell as a factory floor, up to now, we've known some of the 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 among themselves."

The study combined a method of extracting complete protein complexes from cells (tandem affinity purification, developed in 2001 by Bertrand Séraphin at EMBL), mass spectrometry and bioinformatics to investigate the entire protein household of yeast, turning up 257 machines that had never been observed. It also revealed new components of nearly every complex already known.

In the course of the work, new computational techniques were developed at EMBL that gave new insights into the dynamic nature of protein complexes. In contrast to most man-made factories, cells continually dismantle and reassemble their machines at different stages of the cell cycle and in response to environmental challenges, such as infections.

"This would be a logistical nightmare if the cell had to build every machine from scratch any time it needed to do something," says Anne-Claude Gavin, former Director of Molecular and Cell Biology at Cellzome and currently a team leader at EMBL. "We've discovered that the reality is different. Cells use a mixed strateg y 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."

Thus if the cell needs to respond quickly, such as in a disease or another emergency, it may only need to produce few parts to switch on or tune the machine. On the other hand, if something shouldn't happen, it may only need to block the production of a few molecules.

Patrick Aloy and Rob Russell at EMBL used sophisticated computer techniques to reveal the modular organisation of these cellular machines. "This is the most complete set of protein complexes available and probably the set with the highest quality," Aloy says. "Most proteomics studies in the past have shown whether molecules interact or not, in a 'yes/no' way. The completeness of this data lets us see how likely any particular molecule is to bind to another. By combining such measurements for all the proteins in the cell, we discovered new complexes and revealed their modular nature."

"Investigating protein complexes has always posed a tricky problem ?they're too small to be studied by microscopes, and generally too large to be studied by techniques like X-ray crystallography," says Russell. "But they play such a crucial role in the cell that we need to fill in this gap. There's still a huge amount to be learned from this data and from the methods we are developing to combine computational and biochemical investigations of the cell."

"This is an important milestone towards a more global and systems-wide understanding of the cells of organisms ranging from yeast to humans," says Peer Bork, Head of the Structural and Computational Biology Unit at EMBL, and one of the authors of the paper. "Ultimately we hope to achieve a 'molecular anatomy' that takes us from the level of the entire cell to the much deeper level of all the molecules and atoms th at make it up."

Baker's yeast is evolutionary related to the cells of animals and humans, which means that the findings will be more widely applicable. "The same principles discovered here in yeast apply to human cells," says Gitte Neubauer, Vice President at Cellzome. "Drug targets and pathologically relevant proteins are parts of machines and pathways."

The collaboration between Cellzome and EMBL has been very successful, she says, producing fundamental new insights in how molecules are organised and contributing to Cellzome's success in complex and pathway analysis.


Source:European Molecular Biology Laboratory

Related biology news :

1. Study shows how retinoic acid enters a cells nucleus
2. Hopkins researchers discover genetic switch that turns off an oxygen-poor cells combustion engine
3. Johns hopkins researchers find link between cells energy use and genome health
4. Columbia scientists determine 3-dimensional structure of cells fuel gauge
Post Your Comments:

(Date:11/9/2015)... JOSE, Calif. , Nov. 9, 2015  Synaptics ... human interface solutions, today announced broader entry into the ... vehicle-specific solutions that match the pace of consumer electronics ... and biometric sensors are ideal for the automotive industry ... vehicle. Europe , ...
(Date:10/29/2015)... 2015   MedNet Solutions , an innovative SaaS-based ... clinical research, is pleased to announce that it has ... as one of only three finalists for a ... and Growing" category. The Tekne Awards honor Minnesota ... technology innovation and leadership. iMedNet™ eClinical ...
(Date:10/29/2015)... ARBOR, Mich. , Oct. 29, 2015 /PRNewswire/ ... Eurofins Genomics for U.S. distribution of its DNA ... DNA-seq kit and Rubicon,s new ThruPLEX Plasma-seq kit. ... to enable the preparation of NGS libraries for ... plasma for diagnostic and prognostic applications in cancer ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... 2015 --> ... - 2020 report analyzes that automating biobanking workflow ... in long-term samples, minimizing manual errors, improving the ... manual errors such as mislabeling or inaccurate sample ... plays a vital role in blood fractionation, DNA ...
(Date:11/25/2015)... BRUSSELS , November 25, 2015 ... in cat and human plaque and pave the way for ... health problems in cats     ... the most commonly diagnosed health problems in cats, yet relatively ... until now. Two collaborative studies have been conducted by researchers ...
(Date:11/25/2015)... 2015 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS; TSX: ... prospects remain fundamentally strong and highlights the following ... received DSMB recommendation to continue the ZoptEC Phase ... the final interim efficacy and safety data ... men with heavily pretreated castration- and Taxane-resistant prostate ...
(Date:11/25/2015)... , November 25, 2015 ... Report is a professional and in-depth study on ...      (Logo: ) , ... the industry including definitions, classifications, applications and industry ... for the international markets including development trends, competitive ...
Breaking Biology Technology: