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July 28, 2003
Volume 81, Number 30
CENEAR 81 30 p. 13
ISSN 0009-2347


STRUCTURAL BIOLOGY

LOOKING BETWEEN THE SNAPSHOTS
Modeling methods provide insights in ribosome dynamics of motion

CELIA HENRY

When it comes to ribosomes, X-ray crystallography and cryogenic electron microscopy (cryo-EM) only tell part of the story. They provide static snapshots of the endpoints of conformational transitions but not of the transitions themselves.

A team of researchers led by Charles L. Brooks III, a professor of molecular biology at Scripps Research Institute, has used a theoretical method known as elastic-network normal-mode analysis to shed light on what happens during ribosome motions and how those motions are relevant for protein synthesis [Proc. Natl. Acad. Sci. USA, published online July 23, http://www.pnas.org/cgi/doi/10.1073/pnas.1632476100]. Movies showing the motions are available as supporting information within the electronic publication.

Brooks collaborated with Joachim Frank, a Howard Hughes Medical Institute investigator at the State University of New York, Albany, who studies the structure of ribosomes using cryo-EM.

“We have been interested in the mechanical aspects of molecular assemblies for some time,” Brooks says. “The ribosome is a particularly important machine in biology, and we were intrigued by the interesting motions that were suggested by the cryo-EM data. We had hoped that our models would provide a more atomic-level annotation of the transitions suggested by the lower resolution data.”

In the computational method, the ribosome is described as a set of “pseudoatoms.” Rather than every atom being represented in the calculation, the center of each amino acid and nucleotide in the ribosome structure is represented as a single pseudoatom.
“We are using really simplified potentials to do such an analysis,” says lead author Florence Tama, a postdoctoral associate in Brooks’s group. “The simplified potential is mainly capturing the shape of the system.” Using this method, the researchers show that motions deduced from comparisons of cryo-EM maps are well reproduced using the simplified representation.

“The most far-reaching insight is that the ribosome may have gross architectural features that lend themselves to dynamic behavior that is crucial for the basic functions such as translocation,” Frank says. “This makes a lot of sense since the excitation of normal modes is the most efficient way of channeling energy into a required motion.”

“I have been intrigued by the results of normal-mode analysis of ribosomes and the apparent correspondence to different observed states of ribosome structure,” says Harry Noller, who studies ribosomes at the University of California, Santa Cruz. “It could help to explain the high conservation of structural features of the ribosome that appear to be far from any known functional event.”

“In order to understand functional motions of large systems like this, you don’t actually need all the atomic details,” says Robert L. Jernigan, who uses normal-mode analysis to study biological systems at Iowa State University. “These large-domain motions typically depend on the shapes of the structures and not on where the chain of the protein goes within the structure. It’s an argument in favor of electron microscopy over X-ray crystallography.”

DYNAMIC Structural rearrangements of the 70S ribosome are obtained using computational methods. The 30S and 50S subunits are shown in yellow and blue, respectively. The center structure shows the equilibrium conformation of the ribosome. The left and right structures show the ribosome following the rearrangements indicated by the arrows. The red circle and arrow in the right structure indicate the axis of rotation.
© 2003 PNAS



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Charles L. Brooks III

Joachim Frank

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