Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Computational microscope peers into the working ribosome

24.11.2009
Two new studies reveal in unprecedented detail how the ribosome interacts with other molecules to assemble new proteins and guide them toward their destination in biological cells. The studies used molecular dynamics flexible fitting (MDFF) to examine the interaction of the ribosome with two prominent molecular partners.

The first study, in Proceedings of the National Academy of Sciences, concerns the intimate signaling between the ribosome and an elongation factor (EF-Tu) that is essential to the successful assembly of a growing protein. The second, in the journal Structure, focuses on a membrane protein called SecY that sometimes latches onto the ribosome and guides a newly forming protein toward its final destination.

MDFF combines data from two reliable but limited sources of atomic-level information: X-ray crystallography, which can give a high-resolution picture of a single type of molecule, but only in a static, crystal structure; and cryo-electron microscopy (cryo-EM), which can image the dynamic, real-life interaction of two or more molecules in the cell, but at low resolution.

The problem with X-ray crystallography is that the molecules, in this case ribosomes, are artificially removed from the environment of the cell and “packed together like sardines,” said University of Illinois physics professor Klaus Schulten, an author on both papers and principal investigator on the study in Structure. This gives researchers a very detailed image of the components of the ribosome, but offers no clues about its behavior when it encounters other molecules.

Cryo-EM offers a wealth of information about the ribosome in its natural habitat in the cell, but the picture is much less crisp. Like a blurry photograph of a football player maneuvering down the field, cryo-EM gives a general outline, a three-dimensional snapshot of the molecule or molecules of interest at a given point in time, Schulten said.

“It is like a cloud that gives you the volume within which you find 90 percent of all the electrons of the system,” he said. The clouds capture the ribosome in action, but require computing to reveal chemical detail.

The researchers began by building computerized, atomic-scale models of the ribosome-protein complexes based on the crystal structures of the molecules, and then directed the computer to use this information to “fit” the structures into the electron clouds seen in cryo-EM studies. Simulations tracked the behavior of 2.7 million atoms in the SecY study, making it “the biggest, or one of the biggest, computer simulations to be published so far,” Schulten said.

In the first study, the researchers were able to detect the precise molecular maneuvering that allows the ribosome and EF-Tu to recognize and interact with another molecule, transfer-RNA (tRNA). This interaction is key to the successful assembly of proteins because the ribosome and its partners must recognize the tRNA that carries the correct amino acid to be added to the growing protein chain.

The researchers on this study, led by Joachim Frank, of Columbia University (who also provided the cryo-EM data), found structural evidence that when the ribosome recognizes the correct tRNA it induces a change in the shape of EF-Tu. A gate in EF-Tu swings open, allowing a cascade of chemical interactions that lead to the addition of the amino acid to the protein.

The second study provided robust evidence that when the ribosome is translating a membrane protein, or a protein destined for excretion, it hooks up with a single SecY membrane channel shortly after protein translation begins.

The SecY binds to the ribosome by inserting two looped strands into the ribosome’s exit channel. This interaction loosens a plug that normally seals the SecY channel. The plug moves out of the way, allowing the ribosome to funnel the growing protein through the membrane channel.

“We simulated the process of translocation of a (protein) out of the ribosome and into the SecY channel,” said James (J.C.) Gumbart, a postdoctoral researcher at Illinois and first author on the Structure study. “And so we find that even though these loops are inserted into the (ribosome’s) exit tunnel, they are not disturbed, nor do they get in the way of a nascent protein coming out.”

Schulten directs the theoretical and computational biophysics group at the Beckman Institute for Advanced Science and Technology. He and his colleagues pioneered the MDFF approach and, thanks to support from the National Center for Research Resources at the National Institutes of Health, have made its software freely available to more than 160,000 users, he said.

Crystallographers and those doing cryo-EM are enthusiastically embracing MDFF, Schulten said, as this software can be used to tease out the elusive details of otherwise ambiguous data.

In these and other upcoming studies, Schulten and his colleagues are using the computer as a microscope to get a clearer picture of the dynamics of the ribosome, which is perhaps the cell’s most essential, and most complex, molecular machine.

This research on the ribosome is funded through the Center for the Physics of Living Cells, a National Science Foundation Physics Frontiers Center at Illinois, which Schulten co-directs with physics professor and Howard Hughes Medical Institute investigator Taekjip Ha.

Diana Yates | University of Illinois
Further information:
http://www.illinois.edu

More articles from Studies and Analyses:

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

nachricht Urbanization to convert 300,000 km2 of prime croplands
27.12.2016 | Mercator Research Institute on Global Commons and Climate Change (MCC) gGmbH

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>