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 recently in the journal 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 addition to his Medical School post, Ragsdale is a member of the faculty of the U-M Energy Institute.
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."
The research was funded by the National Institutes of Health and the MIT Energy Initiative. Two U.S. Department of Energy-funded synchrotron facilities were used to produce the crystallographic images: the Advanced Photon Source and its Northeastern Collaborative Access Team beamlines supported by NIH, and the Advanced Light Source. The atomic coordinates for the structures published by the team are deposited in the Protein Data Bank under accession codes 4DJD, 4DJE and 4DJF.
Citation: Nature doi:10.1038/nature10916
Kara Gavin | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering