Advanced techniques yield new insights into ribosome self-assembly

Feb 12, 2014
University of Illinois chemistry professor Zaida Luthey-Schulten and physics professor Taekjip Ha led a study of how the ribosome assembles itself. Credit: L. Brian Stauffer

Ribosomes, the cellular machines that build proteins, are themselves made up of dozens of proteins and a few looping strands of RNA. A new study, reported in the journal Nature, offers new clues about how the ribosome, the master assembler of proteins, also assembles itself.

"The ribosome has more than 50 different parts – it has the complexity of a sewing machine in terms of the number of parts," said University of Illinois physics professor Taekjip Ha, who led the research with U. of I. chemistry professor Zaida Luthey-Schulten and Johns Hopkins University biophysics professor Sarah Woodson. "A sewing machine assembles other things but it cannot assemble itself if you have the parts lying around," Ha said. "The ribosome, however, can do that. It's quite amazing."

In 2000, scientists published precise atomic structures of intact ribosomes (a feat that won them a 2009 Nobel Prize in chemistry) and for decades researchers have delved into the mechanics of ribosome function. But scientists have much to learn about how the ribosome itself is built from its component parts, Luthey-Schulten said.

Solving the atomic structure was a huge step forward "that tells us what the ribosome looks like once it's assembled," she said. "But it doesn't tell you anything about how it gets there, how all these parts come together."

All ribosomes consist of two subunits, each a cluster of precisely folded proteins and RNA. The team focused on the small ribosomal subunit of the E. coli bacterium. It is made up of about 20 proteins and a ribosomal RNA (known as 16S).

The researchers labeled one of those ribosomal proteins. Known as S4, it is thought to be the first to interact with the 16S RNA during assembly. They also labeled two sites on the 16S RNA. Each label fluoresced a different color, and was designed to glow more brightly when in close proximity to another label (a technology known as FRET). These signals offered clues about how the RNA and proteins were interacting.

The team was most interested in a central region of the 16s RNA because it contains signature sequences that differentiate the three cellular "domains," or superkingdoms, of life. Previous studies suggested that this region also was key to the RNA- interactions that occur in the earliest stages of ribosome assembly.

Using a "computational microscope," the team compared data from their FRET experiments with an all-atom simulation of the protein and RNA interaction. Their analysis revealed that the S4 protein and the 16S ribosomal RNA were a surprisingly "dynamic duo," Ha said. The protein constrained the RNA somewhat, but still allowed it to undulate and change its conformation.

The team found that the S4 protein tends to bind to the RNA when the RNA takes on an unusual conformation – one not seen in the fully assembled ribosome. This was a surprise, since scientists generally assume that ribosomal proteins lock RNA into its final, three-dimensional shape.

"We found that the S4 and RNA complex is not static," Ha said. "It actually is dynamic and that dynamism is likely to allow binding of the next protein" in the sequence of ribosome assembly.

"Once the S4 binds, it induces other conformational changes that allow the binding sites for other proteins to appear," he said. "So the binding site for the third protein doesn't appear until after the second protein is there."

This intricate dance of molecules leading to the assembly of ribosomes occurs very fast, Luthey-Schulten said. "You can go from as few as 1,000 to 30,000 ribosomes in a bacterial cell during its cell cycle," she said. "More than 80 percent of the RNA that's in the cell is in the ."

Knowing how the ribosome is put together offers new antibiotic targets, said Ha, who is a Howard Hughes Medical Institute investigator and a co-director of the Center for the Physics of Living Cells at Illinois.

"Instead of waiting until your enemy has fully assembled its army, you want to intervene early to prevent that from happening," he said. "We know that this protein/RNA region has unique signatures in bacteria, so maybe we can target this process while keeping the human ribosome intact."

Explore further: Bigger, better, faster: 3D structure reveals protein's Swiss-army knife strategy

More information: "Protein-Guided Dynamics During Early Ribosome Assembly," DOI: 10.1038/nature13039

Related Stories

Mimicking living cells: Synthesizing ribosomes

Jun 29, 2013

Synthetic biology researchers at Northwestern University, working with partners at Harvard Medical School, have for the first time synthesized ribosomes—cell structures responsible for generating all proteins and enzymes ...

Team discovers how a protein finds its way

Apr 29, 2013

( —Proteins, the workhorses of the body, can have more than one function, but they often need to be very specific in their action or they create cellular havoc, possibly leading to disease.

A roundabout route to protein production

Jul 12, 2013

Proteins are typically encoded by linear strands of messenger RNA (mRNA). These mRNA molecules are translated into polypeptide chains by ribosomes, with each ribosomal read-through of the mRNA generating ...

Recommended for you

Researchers successfully clone adult human stem cells

Apr 18, 2014

( —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

Apr 18, 2014

( —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

For resetting circadian rhythms, neural cooperation is key

Apr 17, 2014

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

User comments : 0

More news stories

Biologists help solve fungi mysteries

( —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Researchers successfully clone adult human stem cells

( —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.