Cate Lab Zooms in on the Structure of Protein Factories

CAMBRIDGE, Mass. — Whitehead Associate Member Jamie Cate and his West Coast colleagues have reported on an exciting image of the complete structure, including the moving parts, of an important molecule called the ribosome.

This image zooms in on an intact ribosome—large protein factories found in all cells—at a higher resolution than scientists have ever viewed before. This work builds on previous research in which Jamie provided the first detailed snapshot of a similar ribosome complex but at much lower resolution. The report appeared on the web in Sciencexpress.

Ribosomes read the genetic code and manufacture the corresponding protein. This translation of the genetic code into protein is important because proteins are the workhorses of the body. From the collagen in our skin to the hemoglobin in our blood, proteins carry out the daily tasks that make our bodies function.

Ribosomes are unique catalysts that function differently than the majority of other catalysts found in the cell. Understanding the structural basis of how ribosomes function is essential in explaining why these ancient organelles are unique in their mechanism and may offer clues to understanding life’s origins. The results from the Cate lab may also have implications for developing effective antibiotics, which interfere with bacterial protein synthesis.

In this paper, Jamie and his colleagues were able to get a more complete picture of the ribosome including some of the moving parts that play an important role in the carefully choreographed steps involved in protein synthesis.

As the intact ribosome, composed of two parts, reads the genetic code, molecules known as transfer RNA transport corresponding amino acids into the ribosome and add them to the growing chain of amino acids that will become the protein molecule. After an amino acid is joined to the growing protein, the transfer RNA is released from the ribosome. In a conveyer belt fashion, the protein chain continues to elongate until the genetic message is completely translated.

The Sciencexpress paper is important because it provides a higher resolution atomic structure of the ribosome as a whole with both the genetic message and two transfer RNA molecules bound to it. Although scientists had solved the structure of parts of the ribosome at high resolution, a whole picture remained elusive to scientists until recently.

Using X-ray crystallography, Jamie was able to probe the structure of the complete ribosome, an important step in understanding how it functions. Although ribosomes were first isolated more than 40 years ago, how they work is still essentially a black box, explains Jamie. Many questions about the nature of protein synthesis remain; for example, how do the ribosomes read the genetic code, and how are they regulated?

Jamie has been using X-ray crystallography in an attempt to answer such questions. The technique involves growing crystals of ribosomes, shooting X-rays through those crystals, and collecting diffraction patterns. By gathering phase information about the patterns, Jamie can convert the diffraction patterns into an electron density map of the ribosome.

Ultimately Jamie uses the map, which shows where all of the electrons within the ribosome are located, to build a three-dimensional model of the ribosome. He has been using this process to study ribosomes since his postdoctoral days in Harry Noller's lab at the University of California at Santa Cruz.

Now that he has determined the structure of one particular conformation of the ribosome, Jamie’s next step will involve creating snap shots of other steps in the protein synthesis process by crystallizing other ribosome complexes and determining their structure.

"Having this structure is far from having the complete story," Jamie says. "The ribosome has a lot of moving parts and carefully choreographed steps involved in protein synthesis. Those are what I'm trying to understand."