Featured Research

from universities, journals, and other organizations

Computational microscope peers into the working ribosome

Date:
November 24, 2009
Source:
University of Illinois at Urbana-Champaign
Summary:
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 to examine the interaction of the ribosome with two prominent molecular partners.

The SecY protein channel (grey, green, orange and brown) resides in the membrane.
Credit: Theoretical and Computational Biophysics Group, University of Illinois Beckman Institute.

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.


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Journal References:

  1. Villa et al. Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis. Proceedings of the National Academy of Sciences, 2009; 106 (4): 1063 DOI: 10.1073/pnas.0811370106
  2. James Gumbart, Leonardo G. Trabuco, Eduard Schreiner, Elizabeth Villa, and Klaus Schulten. Regulation of the protein-conducting channel by a bound ribosome. Structure, 17: 1453-1464, 2009 [link]

Cite This Page:

University of Illinois at Urbana-Champaign. "Computational microscope peers into the working ribosome." ScienceDaily. ScienceDaily, 24 November 2009. <www.sciencedaily.com/releases/2009/11/091123132635.htm>.
University of Illinois at Urbana-Champaign. (2009, November 24). Computational microscope peers into the working ribosome. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2009/11/091123132635.htm
University of Illinois at Urbana-Champaign. "Computational microscope peers into the working ribosome." ScienceDaily. www.sciencedaily.com/releases/2009/11/091123132635.htm (accessed September 20, 2014).

Share This



More Plants & Animals News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Chocolate Museum Opens in Brussels

Chocolate Museum Opens in Brussels

AFP (Sep. 19, 2014) Considered a "national heritage" in Belgium, chocolate now has a new museum in Brussels. In a former chocolate factory, visitors to the permanent exhibition spaces, workshops and tastings can discover derivatives of the cocoa bean. Duration: 01:00 Video provided by AFP
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
Raw: Elephant Undergoes Surgery in Tbilisi Zoo

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

AP (Sep. 18, 2014) Grand the elephant has successfully undergone surgery to remove a portion of infected tusk at Tbilisi Zoo in Georgia. British veterinary surgeons used an electric drill to extract the infected piece. (Sept. 18) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins