Chemists concoct new agents to easily study critical cell proteins

Oct 31, 2010 by Terry Devitt

They are the portals to the cell, gateways through which critical signals and chemicals are exchanged between living cells and their environments.

But these gateways -- proteins that span the and connect the world outside the cell to its vital inner workings – remain, for the most part, black boxes with little known about their structures and how they work. They are of intense interest to scientists as they are the targets on which many drugs act, but are notoriously difficult to study because extracting these proteins intact from cell membranes is tricky.

Now, however, a team of scientists from the University of Wisconsin-Madison and Stanford University has devised a technology to more easily obtain for study. Writing this week (Oct. 31) in the journal Nature Methods, the group reports the development of a class of agents capable of extracting complex membrane proteins without distorting their shape, a key to understanding how they work.

"The proteins are embedded in the membrane to control what gets into the cell and what gets out," explains Samuel Gellman, a UW-Madison professor of chemistry and a senior author of the paper along with Brian Kobilka of Stanford and Bernadette Byrne of Imperial College London. "If we want to understand life at the molecular level, we need to understand the properties and functions of these membrane proteins."

The catch with membrane proteins and unleashing their potential, however, is getting insight into their physical properties, says Gellman.

Like other kinds of proteins, membrane proteins exhibit a complex pattern of folding, and determining the three-dimensional shapes they assume in the membrane provides essential insight into how they do business.

Proteins are workhorse molecules in any organism, and myriad proteins are known. Structures have been solved for many thousands of so-called "soluble" proteins, but only a couple of hundred membrane protein structures are known, Gellman notes. This contrast is important because roughly one-third of the proteins encoded in the human genome appear to be membrane proteins.

To effectively study a , scientists must have access to it. A primary obstacle has been simply getting proteins out of the membrane while maintaining their functional shapes. To that end, Gellman's group has developed a family of new chemical agents, known as amphiphiles, that are easily prepared, customizable to specific proteins and cheap.

"These amphiphiles are very simple," says Gellman. "That's one of their charms. The other is that they can be tuned to pull out many different kinds of proteins."

The hope, according to Gellman, is that the new technology will facilitate research at the biomedical frontier.

The development of the amphiphiles was conducted in close collaboration with groups like Kobilka's, which specializes in techniques that help resolve the three-dimensional structures of proteins found in cell membranes.

Explore further: Conjecture on the lateral growth of Type I collagen fibrils

Related Stories

Instruction Manual for Creating a Molecular Nose

Feb 12, 2007

An artificial nose could be a real benefit at times: this kind of biosensor could sniff out poisons, explosives or drugs, for instance. Researchers at the Max Planck Institute for Polymer Research and the Max ...

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 ...

The future of drug development

Sep 03, 2010

John Engen, associate professor of chemistry and chemical biology at the Northeastern University, is at the forefront of research that will advance drug discovery and development by making it easier to analyze ...

Recommended for you

Conjecture on the lateral growth of Type I collagen fibrils

Sep 12, 2014

Whatever the origin and condition of extraction of type I collagen fibrils, in vitro as well as in vivo, the radii of their circular circular cross sections stay distributed in a range going from 50 to 100 nm for the most ...

Chemists create 'assembly-line' for organic molecules

Sep 11, 2014

(Phys.org) —Scientists at the University of Bristol have developed a process where reagents are added to a growing carbon chain with extraordinary high fidelity and precise orientation, thereby controlling ...

User comments : 0