New discovery blurs distinction between human cells and those of bacteria

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

“This is the first look at how microcompartments are built, and what the pieces look like,” said Todd O. Yeates, UCLA professor of chemistry and biochemistry, and a member of the UCLA-DOE Institute of Genomics and Proteomics. “These microcompartments appear to be highly evolved machines, and we are just now learning how they are put together and how they might work. We can see the particular amino acids and atoms.”

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

“Students who take a biology class learn in the first three days 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 of a continuum than a sharp divide. These microcompartments, which resemble viruses because they are built from thousands of protein subunits assembled into a shell-like architecture, are an important component of bacteria. I expect there will be a much greater focus on them now.”

Yeates’ Science paper reveals the first structures of the proteins that make up these shells, and the first high-resolution insights into how they function.

“Those microcompartments have remained shrouded in mystery, largely because of an absence of a detailed understanding of their architecture, of what the structures look like,” said Yeates, who also is a member of the California NanoSystems Institute and UCLA’s Molecular Biology Institute. “The complete three-dimensional structure is still unknown, but in this paper we have provided 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 that presumably do similar things in 50 other bacteria, Yeates said.

“Our findings blur the distinction between eukaryotic cells and those of prokaryotes by arguing that bacterial cells are more complex than one would imagine, and that many of them have evolved sophisticated mechanisms,” Yeates said.

While microcompartments have been directly observed in only a few organisms, “surely there will be many more,” Yeates said. “The capacity to create subcellular compartments is very widespread across diverse microbes. We believe that many prokaryotes have the capacity to create subcellular compartments to 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 Hughes Medical Institute; Shiho Tanaka, a former UCLA undergraduate who is starting graduate work at UCLA this fall in biochemistry; and UCLA chemistry and biochemistry graduate student Morgan 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 the space between them. If you take six pennies and place them in the shape of a ring, that leaves a large space in the middle. Yet the shape of this protein molecule is such that when six proteins come together, they nearly fill the space; what struck me is how tightly packed they are. That tells us the shell plays an important role in controlling what comes in and goes out. When we saw how the many hexagons come together, we saw that they filled the space tightly as well.”

The UCLA biochemists determined the structures from their analysis of small crystals, using X-ray crystallography. How microcompartments 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.