1. Home
  2. News & Publications
  3. Research News

Jul. 26, 2013 Research Highlight Biology

A roundabout route to synthesis

In-depth analysis of an amino acid-synthesizing enzyme reveals a ring-shaped structure with numerous unusual characteristics

Every protein in every organism is composed of different combinations of the same 20 amino acids. During protein synthesis, each of these amino acids is delivered to the ribosome by a specific transfer RNA (tRNA) molecule. This list of ‘ingredients’, however, can be expanded to include additional ‘non-canonical’ amino acids. Researchers led by Shigeyuki Yokoyama of the Structural Biology Laboratory have now uncovered the sophisticated mechanism by which bacteria generate the non-canonical amino acid selenocysteine (Sec)1.

Most amino acids are joined to their ‘partner’ tRNA by specialized enzymes. However, Sec lacks such an enzyme so its tRNA (tRNASec) is instead linked to the amino acid serine (Ser), which is then converted to Sec by selenocysteine synthase (SelA). SelA must therefore be able to identify when Ser is linked to tRNASec rather than its normal partner tRNA, tRNASer. To investigate this mechanism, Yokoyama’s team performed an in-depth structural analysis of SelA from the bacterium Aquifex aeolicus, and collaborated with Dieter Söll’s group at Yale University in the US to perform functional analysis of SelA.

The researchers' data revealed an elaborate configuration of ten identical SelA subunits, arranged into a ring of five discrete SelA pairs (Fig. 1). Each Ser-tRNASec molecule interacts with two SelA subunit pairs; one pair contributes to tRNASec recognition, while the other is responsible for catalyzing Ser-to-Sec conversion. Remarkably, each ten-subunit SelA can bind ten Ser-tRNASec molecules, indicating a complex yet efficient network of interactions.

“The arrangement of the four subunits enables each of them to do its specific task, which differs from that of the other three subunits,” says Yokoyama. “This pattern of collaboration among four subunits is repeated ten times on the ring.”

Eukaryotic and archaeal species also have specialized enzymes, known as ‘SepSecS’, that catalyze Sec synthesis, but the researchers were surprised to note that these enzymes bear virtually no resemblance to bacterial SelA. This suggests that these organisms each arrived at their own solution to a shared biochemical problem. “These two systems emerged completely independently of each other in the evolution of life,” says Yokoyama. During this process, SelA acquired distinctive features that allow it to accurately differentiate between tRNASec and tRNASer, and to assume the unique ‘decameric’ structure that sets it apart from other structurally related proteins.

“The huge structure of the SelA•tRNASec complex has provided an abundance of remarkable surprises,” concludes Yokoyama. His team is now striving to obtain even more detailed structural information that might offer additional insight into how this unusual cellular machine functions.

Image of SelA enzyme Figure 1: The SelA enzyme assembles into a complex ring-shaped structure that allows it to efficiently process up to ten Ser-tRNASec molecules at a time. © 2013 AAAS

References

  • 1. Itoh, Y., Bröcker, M. J., Sekine, S., Hammond, G., Suetsugu, S., Söll, D. & Yokoyama, S. Decameric SelA•tRNASec ring structure reveals mechanism of bacterial selenocysteine formation. Science 340, 75–78 (2013). doi: 10.1126/science.1229521

Top