Scientists devise method to study membrane proteins

Apr 14, 2004

Scientists at the University of Virginia Health System have come up with a protocol to extract proteins from membranes by using chemicals that allow them to be reversibly folded and refolded. The proteins can then be studied using crystallography or nuclear magnetic resonance imaging. Their work is detailed in the March 23 issue of the “Proceedings of the National Academy of Sciences” (PNAS) and also on the cover of the journal. The paper can be found on the web at: http://www.pnas.org/cgi/content/full/101/12/4065.

“The majority of drugs on the market today are effective because they work on membrane proteins, but our basic knowledge about these proteins lags far behind that of water-soluble proteins,” said Lukas Tamm, professor of molecular physiology and biological physics at U.Va. “We need to develop systems to get enough of these membrane proteins expressed in a cell culture so we can measure their thermodynamic, or energetic, stability,” Tamm said. “This is of practical interest in designing proteins for therapeutic applications because the proteins need to be kept around for a long time. This protocol developed at U.Va. shows for the first time that these proteins can be taken out of their membrane environment and put back in without losing function,” Tamm said. “We also found that the thermodynamic stability, or energy difference, between the folded and unfolded form of membrane proteins depends on the strength of the membrane “rubber band” that the proteins sit in. This energy difference can be predicted, one key variable in the drug discovery process.”

In a commentary on the findings, also in the March 23 issue of PNAS, James Bowie, a professor with the Molecular Biology Institute at the University of California, Los Angeles, wrote that “the new work opens another door to a more quantitative description of the energetics protein-protein and protein-lipid interactions in the (membrane) bilayer… We are finally beginning to obtain quantitative information about membrane protein structure.”

Working with U.Va. colleague Heedeok Hong, Tamm used an aqueous (water) system and a compound called urea, that unravels proteins, to carry out folding studies on a membrane protein of the Escherichia coli bacterium called OmpA. Tamm and Hong demonstrated that the folding of OmpA into the lipid bilayers of a membrane is a reversible, two-state process. They also demonstrated that elastic forces in bilayers, such as curvature stress, can affect the folding of membrane proteins.


Explore further: New approach to form non-equilibrium structures

add to favorites email to friend print save as pdf

Related Stories

Putin signs law seen as crimping social media

15 minutes ago

President Vladimir Putin on Tuesday signed a law requiring Internet companies to store all personal data of Russian users at data centres in Russia, a move which could chill criticism on foreign social networking ...

New launch date set for ISS delivery vessel

24 minutes ago

A robot ship will be launched from Kourou, French Guiana, after a five-day delay on July 29 to deliver provisions to the International Space Station, space transport firm Arianespace said Tuesday.

P90X? Why consumers choose high-effort products

40 minutes ago

Stuck in traffic? On hold for what seems like an eternity? Consumers often face situations that undermine their feelings of control. According to a new study in the Journal of Consumer Research, when a person's sense of con ...

Recommended for you

First in-situ images of void collapse in explosives

3 hours ago

While creating the first-ever images of explosives using an x-ray free electron laser in California, Los Alamos researchers and collaborators demonstrated a crucial diagnostic for studying how voids affect ...

New approach to form non-equilibrium structures

23 hours ago

Although most natural and synthetic processes prefer to settle into equilibrium—a state of unchanging balance without potential or energy—it is within the realm of non-equilibrium conditions where new possibilities lie. ...

User comments : 0