Breakthrough: Scientists Create 3-D Map Of Cell Membrane Ion Pump At Near Atomic Resolution

Their work is a basic science breakthrough, the investigators say, because of the great difficulty involved and the importance of membranes, which control many key bodily functions.

"Before you can understand how something in the body works, you have to know what its structure is at the atomic level, and that's what we have been investigating," said Dr. Gene A. Scarborough, professor of pharmacology at the University of North Carolina at Chapel Hill School of Medicine. "The ion pump we studied is especially important because it is part of a family of membrane proteins that regulate blood pressure, heart function, nerve conduction and acid secretion."

A report on the findings just appeared in Nature, the top British biological journal. Besides Scarborough, authors are Dr. Manfred Auer and Werner Kuhlbrandt of the Max Planck Institute for Biophysics in Frankfurt, Germany.

"Membranes and the pumps within them are important because they help keep the good stuff inside cells and the bad stuff out," Scarborough said. "But to see the structure of membrane pumps, you have to crystallize them. That is what we have done, and we are getting very close to atomic resolution."

In creating their 3-D "map," the researchers used a detergent-like compound to overcome a stubborn technical difficulty. The problem was that unlike most other proteins, cell membrane proteins are embedded in a natural greasy substance that makes growing crystals of them nearly impossible.

By a clever strategy, Scarborough succeeded in getting the soapy substance and the protein to crystallize together - an approach that he said could be useful for crystallizing other membrane proteins as well.

"Under the microscope, these proteins look something like a tree or complicated piece of driftwood," Scarborough said. "In cross section, they form a beautiful hexagonal array that looks something like a honeycomb."

Knowing the exact structure of the membrane protein, called H+-ATPase, will help researchers better understand how these pumps act to control the flow of ions, or charged particles, of such critical elements as sodium, potassium and calcium.

"Although as basic scientists we are not so much concerned with applications of our work, detailed understanding of this medically significant membrane protein family may open the door to drugs that can regulate these molecules in disease states," the biochemist said.

In recognition of his continuing experiments, the Alexander von Humboldt Foundation last month awarded Scarborough one of its prestigious $80,000 Humboldt prizes to pay for travel and other personal expenses associated with his research.

"Few scientists study plasma membrane proteins because compared with other proteins, they are so difficult to work with," he said. The new report appeared in the April 23 issue of Nature.