Understanding How Microbes Sequester Potentially Deadly Metabolites

The Science

Living cells use precise control processes to regulate critical metabolic processes. Sometimes cells produce volatile or potentially damaging byproducts that need to be sequestered to protect the cells. Scientists at the University of California–Los Angeles/DOE Institute for Genomics and Proteomics have discovered the structure of an important type of microcompartment in microbial cells that enables ethanolamine to be metabolized without releasing the volatile intermediate, acetaldehyde. They determined the structures of the four proteins that make up the walls of the microcompartment and used this information to discover how the combined structures enable selective transport across the walls to protect the microbe from toxic damage.

The three-dimensional (3D) crystal structures, with resolutions between 1.65 and 2.5 angstroms, of the four homologous proteins (EutS, EutL, EutK, and EutM) that are thought to be the major shell constituents of a functionally complex ethanolamine utilization (Eut) microcompartment. The Eut microcompartment is used to sequester the metabolism of ethanolamine in bacteria such as Escherichia coli and Salmonella enterica. The four Eut shell proteins share an overall similar 3D fold, but they have distinguishing structural features that help explain the specific roles they play in the microcompartment. For example, EutL undergoes a conformational change that is probably involved in gating molecular transport through shell protein pores, whereas structural evidence suggests that EutK might bind a nucleic acid component.

Together these structures give mechanistic insight into bacterial microcompartments. The understanding gained in the research could enable design of nanoparticles using proteins modified to enhance production of molecules for biofuels and other applications.

Summary

In diverse bacteria, reactions that involve toxic or volatile metabolites are carried out by enzymes inside proteinaceous microcompartments. This research team reports high-resolution crystal structures for four homologous proteins that are constituents of the shell that sequesters the metabolism of ethanolamine in bacteria. While the structures have similar overall folds, they have distinctive structural features that provide insight into how they build the shell and participate in microcompartment function.

Principal Investigator

Todd O. Yeates
University of California–Los Angeles

BER Program Manager

U.S. Department of Energy, Biological and Environmental Research (SC-33)
Biological Systems Science Division
[email protected]

References

Tanaka, S., M. R. Sawaya and T.O. Yeates. 2010. “Structure and Mechanisms of a Protein-Based Organelle in Escherichia coli,” Science 327(1), 81–4. DOI:10.1126/science.1179513.