Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Insights Into Protein Synthesis and Hepatitis C Infections

05.12.2005


Scientists have uncovered key new information towards understanding the crucial first step in protein synthesis, the process by which the genetic code, harbored within DNA and copied into RNA, is translated into the production of proteins. This new information also helps to explain how viruses, such as Hepatitis C, are able to highjack protein synthesis machinery in humans for their own purposes.



Biochemist Jennifer Doudna and biophysicist Eva Nogales, both of whom hold joint appointments with the Lawrence Berkeley National Laboratory (Berkeley Lab), the University of California at Berkeley, and the Howard Hughes Medical Institute (HHMI), led a study in which cryo electron microscopy (cryo-EM) was used to create a 3-D model of the protein complex called eukaryotic translation initiation factor 3 (eIF3). The model showed that the eIF3 protein complex employs the same structural mechanics in the loading of either human or viral RNA to ribosomes, the complex machinery in living cells responsible for protein synthesis.

“This is the first insight into how the initiation mechanisms of protein synthesis work specifically for humans, and a step towards understanding at the molecular level what happens when a viral infection occurs,” said Doudna, a member of Berkeley Lab’s Physical Biosciences Division. “A better understanding of these mechanisms could open the door to new and improved therapies for viral infections.”


Said Nogales, also a member of Berkeley Lab’s Physical Biosciences Division, “Using cryo-EM, we can reconstruct images of the entire protein ensemble to study the molecular machinery behind the protein synthesis process. We now have the tools to see how the many different parts of the molecular machinery come together.”

The results of this study are in the December 2, 2005 issue of the journal Science, in a paper entitled: Structural Roles for Human Translation Factor eIF3 in Initiation of Protein Synthesis. Co-authoring the paper with Doudna and Nogales were Bunpote Siridechadilok and Christopher Fraser of UC Berkeley, and Richard Hall of Berkeley Lab.

Proteins, the curiously-shaped macromolecules that serve as the basic construction material of all living cells, and also initiate and control nearly all cell chemistry, are assembled out of amino acids according to the instructions contained within the genes. These genetic instructions are carried from the DNA inside a cell’s nucleus out into the cell’s cytoplasm via messenger RNA (mRNA). There the information will be translated to a sequence of amino acids via the ribosome, an ancient organelle so highly conserved by evolution that its core components are pretty much the same for all forms of life.

Protein synthesis in mammalian cells begins with the loading of mRNA onto the small ribosome subunit, 40S, which is, in part, one of the responsibilities of the eIF3 complex. The eIF3 complex also interacts with other translation elements that bind at the start of the mRNA, prevents premature joining of the 40S and 60S ribosomal subunits, and helps assemble active ribosomes. Until now, the structural basis for eIF3’s multiple activities has been unknown.

At a resolution of 30 angstroms, the cryo-EM reconstructions of Doudna and Nogales and their collaborators show eIF3 to be a particle consisting of five lobes - analogous to a head, and a pair of arms and legs. The study shows that the left arm of the eIF3 complex binds to the eukaryotic protein complex that recognizes the methylated guanosine cap at the 5’-end of the eukaryotic mRNAs (mRNA consists of a coding region sandwiched between a 5’-end and a 3’-end). By drawing the mRNA’s 5’-end cap through the ribosome entry site and towards the exit, eIF3 ensures the mRNA is properly positioned for its genetic code to be translated.

Acting like a molecular wrestler, eIF3 will also wrap its arms and legs around a structural element of RNA for the hepatitis C virus (HVC), known as the internal ribosome entry site (IRES), and pin it to the exit site of the 40S ribosome subunit. The IRES leaves through the left arm of the eIF3 complex at the same location where interaction with the human mRNA cap-binding complex takes place.

“This might explain the amazing ability of the HVC IRES to hijack the human ribosome and its associated translation factors,” said Doudna.

Said Nogales, “The position of eIF3 in our models also provides a plausible explanation for its role in preventing premature joining of the 40S and 60S ribosome subunits.”

Doudna and members of her research group are now working to improve the resolution of these models from 30 angstroms to about 10 angstroms. This would allow them to see secondary protein structures which would give them a better understanding of the chemistry behind eIF3’s structural mechanics.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California.

Lynn Yarris | EurekAlert!
Further information:
http://www.lbl.gov/Science-Articles/Archive/LSD-protein-synthesis.html
http://www.lbl.gov

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>