New Discovery Blurs Distinction Between Human Cells And Those Of Bacteria

"This is the first look at how microcompartments are built, and whatthe pieces look like," said Todd O. Yeates, UCLA professor of chemistryand biochemistry, and a member of the UCLA-DOE Institute of Genomicsand Proteomics. "These microcompartments appear to be highly evolvedmachines, and we are just now learning how they are put together andhow they might work. We can see the particular amino acids and atoms."

A key distinction separating the cells of primitive organismslike bacteria, known as prokaryotes, from the cells of complexorganisms like humans is that complex cells -- eukaryotic cells -- havea much higher level of subcellular organization; eukaryotic cellscontain membrane-bound organelles, such as mitochondria, the tiny powergenerators in cells. Cells of prokaryotes have been viewed as veryprimitive, although some contain unusual enclosures known asmicrocompartments, which appear to serve as primitive organelles insidebacterial cells, carrying out special reactions in their interior.

"Students who take a biology class learn in the first threedays that cells of prokaryotes are uniform and without organization,while cells of eukaryotes have a complex organization," Yeates said."That contrast is becoming less stark; we are learning there is more ofa continuum than a sharp divide. These microcompartments, whichresemble viruses because they are built from thousands of proteinsubunits assembled into a shell-like architecture, are an importantcomponent of bacteria. I expect there will be a much greater focus onthem now."

Yeates' Science paper reveals the first structures of theproteins that make up these shells, and the first high-resolutioninsights into how they function.

"Those microcompartments have remained shrouded in mystery,largely because of an absence of a detailed understanding of theirarchitecture, of what the structures look like," said Yeates, who alsois a member of the California NanoSystems Institute and UCLA'sMolecular Biology Institute. "The complete three-dimensional structureis still unknown, but in this paper we have provided the firstthree-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 that presumably do similar things in 50 other bacteria, Yeates said.

"Our findings blur the distinction between eukaryotic cells andthose of prokaryotes by arguing that bacterial cells are more complexthan one would imagine, and that many of them have evolvedsophisticated mechanisms," Yeates said.

While microcompartments have been directly observed in only afew organisms, "surely there will be many more," Yeates said. "Thecapacity to create subcellular compartments is very widespread acrossdiverse microbes. We believe that many prokaryotes have the capacity tocreate subcellular compartments to organize their metabolicactivities."

Yeates' research team includes research scientist and leadauthor Cheryl Kerfeld; Michael Sawaya, a research scientist with UCLAand the Howard Hughes Medical Institute; Shiho Tanaka, a former UCLAundergraduate who is starting graduate work at UCLA this fall inbiochemistry; and UCLA chemistry and biochemistry graduate studentMorgan Beeby.

The structure of the carboxysome shows 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 six protein molecules fill thespace between them. If you take six pennies and place them in the shapeof a ring, that leaves a large space in the middle. Yet the shape ofthis protein molecule is such that when six proteins come together,they nearly fill the space; what struck me is how tightly packed theyare. That tells us the shell plays an important role in controllingwhat comes in and goes out. When we saw how the many hexagons cometogether, we saw that they filled the space tightly as well."

The UCLA biochemists determined the structures from theiranalysis of small crystals, using X-ray crystallography. Howmicrocompartments fold into their functional shapes remains a mystery.

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

If microcompartments can be engineered, biotechnology applications potentially could arise from this research, Yeates said.

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