Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Structure reveals how cells 'sugar-coat' proteins

13.03.2008
Biologists at the U.S. Department of Energy's Brookhaven National Laboratory, Stony Brook University, and the University of Wurzburg, Germany, have deciphered the structure of a large protein complex responsible for adding sugar molecules to newly formed proteins - a process essential to many proteins' functions.

The structure offers insight into the molecular "sugar-coating" mechanism, and may help scientists better understand a variety of diseases that result when the process goes awry. The research will appear in the March 12, 2008, issue of the journal Structure.

"Proteins perform their functions by interacting at their surfaces with other molecules. So you can imagine that adding or removing sugar molecules will change the protein's surface structure, and therefore its function," said Huilin Li, a biologist at Brookhaven Lab who holds a joint appointment at Stony Brook and is co-corresponding author on the Structure paper. "Messing up this process can lead to the production of malformed proteins that are unable to do their jobs," he added.

The results can be devastating. Failure of glycosylation, as the "sugar-coating" process is known, can lead to a variety of genetic disorders characterized by neurological problems including seizures and stroke-like episodes, feeding disorders, and possibly even some forms of muscular dystrophy.

"We studied one enzyme involved in glycosylation, the one that recognizes the protein sequence and adds the sugar chains to the protein as it is being synthesized by the cell," said William J. Lennarz of Stony Brook University, a coauthor on the paper. "The challenge is that the enzyme, known as oligosaccharide transferase (OT), is large by protein standards, has eight intricately linked components, and sits embedded in a membrane within the cell's protein-manufacturing machinery."

"Membrane proteins, particularly large ones, are very difficult to study structurally," added Li.

So the scientists turned to a technique called cryo-electron microscopy (cryo-EM), which shows great promise in deciphering large membrane protein structures.

"We imaged the purified OT complex by cryo-EM and obtained a first snapshot of the complex by computer reconstruction of the micrographs," said Li, a cryo-EM expert.

In cryo-EM, he explained, samples are frozen in vitreous ice and maintained at cryogenic temperatures (-274° Fahrenheit) using liquid nitrogen while the samples are photographed in the high vacuum of an electron microscope. The sophisticated cryo-EM machine resides in Brookhaven Lab's biology department. Li and his collaborators also measured the mass of the OT complex at Brookhaven's Scanning Transmission Electron Microscope (STEM) facility.

The structure deciphered by the group helps to explain many biochemical phenomena observed about the enzyme complex over the past two decades. It also offers hints as to how the enzyme performs its various jobs, from recognizing the sugar molecules to be added to the protein, scanning the protein as it is formed to identify the sites where sugars should be attached, and transferring the sugar molecules to the protein at the right positions.

"OT physically associates with the protein translocation channel which moves a protein across a membrane and the cell's protein synthesis machinery, forming an efficient three-machine assembly line for protein translation, translocation, and glycosylation," Li said.

The researchers say further research is needed to illuminate the molecular mechanisms of disorders of glycosylation involving oligosaccharide transferase. For example, they would like to do structural studies of the enzyme at higher resolution in complex with substrates or in association with the cell's protein translocation and protein synthesis machinery. A new facility Brookhaven Lab hopes to begin construction on next year, known as the National Synchrotron Light Source II, would greatly increase the precision of this work.

Karen McNulty Walsh | EurekAlert!
Further information:
http://www.bnl.gov
http://www.bnl.gov/newsroom

Further reports about: Brookhaven Complex cryo-EM enzyme glycosylation structure sugar

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>