Science + Technology

UCLA Biochemists Provide First Structural Details of Mysterious Bacterial Microcompartments

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UCLA biochemists revealthe first structural details of a family of mysterious objects called microcompartments that seem to be present in a variety ofbacteria. The discovery was published Aug. 5 in the journal Science.

"This is the first look at how microcompartments arebuilt, and what the pieces look like," said Todd O. Yeates, UCLA professor of chemistry and biochemistry, and amember of the UCLA-DOE Institute of Genomics and Proteomics. "These microcompartments appear tobe highly evolved machines, and we are just now learning how they areput together and how they might work. We can see the particular amino acids andatoms."

A key distinction separating the cells of primitiveorganisms like bacteria, known as prokaryotes, from the cells of complex organismslike humans is that complex cells —eukaryotic cells — have a much higher level of subcellularorganization; eukaryotic cells contain membrane-bound organelles, such as mitochondria,the tiny power generators in cells. Cells of prokaryoteshave been viewed as very primitive, although some contain unusual enclosuresknown as microcompartments, which appear to serve as primitive organelles insidebacterial cells, carrying out special reactions in their interior.

"Students who take a biology classlearn in the first three days that cells of prokaryotes areuniform and without organization, while cells of eukaryotes have a complexorganization," Yeates said. "That contrast isbecoming less stark; we are learning there is more of a continuum than a sharpdivide. These microcompartments,which resemble viruses because they are built from thousands of proteinsubunits assembled into a shell-like architecture, are an important componentof bacteria. I expect there will be a much greater focus on them now."

Yeates' Science paper reveals the first structures of the proteins thatmake up these shells, and the first high-resolution insights into how theyfunction.

"Those microcompartments have remainedshrouded in mystery, largely because of an absence of a detailed understandingof their architecture, of what the structures look like," said Yeates, who also is a member of theCalifornia NanoSystemsInstitute and UCLA's Molecular Biology Institute. "The completethree-dimensional structure is still unknown, but in this paper we haveprovided the first three-dimensional structure of the building blocks of the carboxysome, a protein shell which is the best-studied microcompartment."

The UCLA biochemists also report 199 related proteins thatpresumably do similar things in 50 other bacteria, Yeatessaid.

"Ourfindings blur the distinction between eukaryoticcells and those of prokaryotes by arguing that bacterial cells are morecomplex than one would imagine, and that many of them have evolvedsophisticated mechanisms," Yeates said.

Whilemicrocompartments have been directly observed in only a few organisms,"surely there will be many more," Yeates said. "Thecapacity to create subcellular compartments is verywidespread across diverse microbes. We believe that many prokaryoteshave the capacity to create subcellular compartmentsto organize their metabolic activities."

Yeates' research team includes research scientist and lead author Cheryl Kerfeld; Michael Sawaya, a research scientist with UCLA and the Howard HughesMedical Institute; Shiho Tanaka, a former UCLA undergraduate who is startinggraduate work at UCLA this fall in biochemistry; and UCLA chemistry and biochemistry graduate student Morgan Beeby.

Thestructure of the carboxysomeshows a repeating pattern of six protein molecules packed closely together.

"We didn't know six would be the magic number," Yeates said. "What surprises me is how nearly these sixprotein molecules fill the space between them. If you take six pennies andplace them in the shape of a ring, that leaves a large space in the middle. Yetthe shape of this protein molecule is such that when six proteins cometogether, they nearly fill the space; what struck me is how tightly packed theyare. That tells us the shell plays an important role in controlling what comesin and goes out. When we saw how the many hexagons come together, we saw thatthey filled the space tightly as well."

TheUCLA biochemists determined the structures from their analysis of smallcrystals, using X-ray crystallography. How microcompartments fold into their functional shapes remains a mystery.

Yeates'laboratory will continue to study the structures of microcompartmentsfrom other organisms.

If microcompartmentscan be engineered, biotechnology applications potentially could arise from thisresearch, Yeates said.

The research was federally funded by the U.S.Department of Agriculture, the National Institutes of Health and the U.S.Department of Energy.

-UCLA-

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