In research that could one day lead to advances against neurodegenerative diseases like Alzheimer's and Parkinson's, University of Michigan engineering researchers have demonstrated a technique for precisely measuring the properties of individual protein molecules floating in a liquid. Prot ... more
Vitamins doing gymnastics: Scientists capture first full image of vitamin B12 in actionWork by University of Michigan and MIT team yields new understanding of crucial reaction in the body and in CO2-scrubbing bacteria
You see it listed on the side of your cereal box and your multivitamin bottle. It's vitamin B12, part of a nutritious diet like all those other vitamins and minerals. But when it gets inside your body, new research suggests, B12 turns into a gymnast.
In a paper published in Nature, scientists from the University of Michigan Health System and the Massachusetts Institute of Technology report they have created the first full 3-D images of B12 and its partner molecules twisting and contorting as part of a crucial reaction called methyltransfer.
That reaction is vital both in the cells of the human body and, in a slightly different way, in the cells of bacteria that consume carbon dioxide and carbon monoxide. That includes bacteria that live in the guts of humans, cows and other animals, and help with digestion. The new research was done using B12 complexes from another type of carbon dioxide-munching bacteria found in the murky bottoms of ponds.
The 3-D images produced by the team show for the first time the intricate molecular juggling needed for B12 to serve its biologically essential function. They reveal a multi-stage process involving what the researchers call an elaborate protein framework – a surprisingly complicated mechanism for such a critical reaction.
U-M Medical School professor and co-author Stephen Ragsdale, Ph.D., notes that this transfer reaction is important to understand because of its importance to human health. It also has potential implications for the development of new fuels that might become alternative renewable energy sources.
"Without this transfer of single carbon units involving B12, and its partner B9 (otherwise known as folic acid), heart disease and birth defects might be far more common," explains Ragsdale, a professor of biological chemistry. "Similarly, the bacteria that rely on this reaction would be unable to consume carbon dioxide or carbon monoxide to stay alive – and to remove gas from our guts or our atmosphere. So it's important on many levels."
In such bacteria, called anaerobes, the reaction is part of a larger process called the Wood-Ljungdahl pathway. It's what enables the organisms to live off of carbon monoxide, a gas that is toxic to other living things, and carbon dioxide, which is a greenhouse gas directly linked to climate change. Ragsdale notes that industry is currently looking at harnessing the Wood-Ljungdahl pathway to help generate liquid fuels and chemicals.
In the images created by the team, the scientists show how the complex of molecules contorts into multiple conformations - first to activate, then to protect, and then to perform catalysis on the B12 molecule. They had isolated the complex from Moorella thermoacetica bacteria, which are used as models for studying this type of reaction.
The images were produced by aiming intense beams of X-rays at crystallized forms of the protein complex and painstakingly determining the position of every atom inside.
"This paper provides an understanding of the remarkable conformational movements that occur during one of the key steps in this microbial process, the step that involves the generation of the first in a series of organometallic intermediates that lead to the production of the key metabolic intermediate, acetyl-CoA," the authors note.
Senior author Catherine L. Drennan from MIT and the Howard Hughes Medical Institute, who received her Ph.D. at the U-M Medical School, adds, "We expected that this methyl-handoff between B vitamins must involve some type of conformational change, but the dramatic rearrangements that we have observed surprised even us."
- University of Michigan
- vitamin B12
Lupus, a chronic autoimmune disease, can wreak havoc on an affected individual's body through inflammation, pain and even damage of the skin, joints and organs. To try to better understand how the disease begins and progresses, researchers at the University of Michigan investigated whether ... more
One of the earliest widespread applications of precision medicine in cancer care is helping patients and physicians decide whether chemotherapy is needed, a new study finds. Researchers looked at a test available to help assess the risk of breast cancer recurrence and whether chemotherapy i ... more
A new molecular gel recipe developed at the University of Michigan by Anne McNeil, Arthur F Thurnau Professor of Macromolecular Science, and is at the core of a prototype for a more accurate lead paint test.The new test is more clear and accurate than its counterparts. It consists of a vial ... more
For the first time ever, a single flexible fiber no bigger than a human hair has successfully delivered a combination of optical, electrical, and chemical signals back and forth into the brain, putting into practice an idea first proposed two years ago. With some tweaking to further improve ... more
The Semiconductor Industry Association has estimated that at current rates of increase, computers’ energy requirements will exceed the world’s total power output by 2040. Using light rather than electricity to move data would dramatically reduce computer chips’ energy consumption, and the p ... more
A new, specially coated iron oxide nanoparticle developed by a team at MIT and elsewhere could provide an alternative to conventional gadolinium-based contrast agents used for magnetic resonance imaging (MRI) procedures. In rare cases, the currently used gadolinium agents have been found to ... more