HHMI investigator Roderick MacKinnon is studying the cell's plasma membrane by zooming out to look at all its components together, rather than going the traditional route of isolating individual proteins.

“We're in a very, very primitive stage of understanding the membrane,” says HHMI investigator Roderick MacKinnon at Rockefeller University. “We've been looking at the membrane in a very protein-centric way and we have to understand it with a more holistic view of all its components.”

For a long time, the immediate challenge was to figure out the structure and function of the membrane proteins, which do most of the communicating and transporting. But the proteins tend to fall apart when removed from the membrane for study. In 1998, however, MacKinnon published the first structure of an ion channel—a protein that acts as a conduit for potassium through the membrane. Ion channels allow cells to generate, and pass along, electrical signals by controlling the flow of charged potassium, sodium, and calcium molecules through the membrane.

MacKinnon's structural breakthrough earned him, along with Peter Agre of the Johns Hopkins University School of Medicine, the 2003 Nobel Prize in Chemistry and shattered the long-held notion that determining the structure of channels was an insurmountable challenge. In the decade since, the structures of more than 200 membrane proteins have been solved and scientists are moving on to study the finer details of how the proteins function and interact with the membrane.

MacKinnon and other HHMI investigators, while still adding to the growing list of membrane protein structures, are also beginning to look at the membrane as a whole. They're studying proteins in the membranes, rather than isolated in solution, and asking questions about how different membrane elements interact with each other and with proteins. They're hoping to uncover what goes on at the boundary of the cell.

The simple fact that oil and water don't mix guides much of membrane science. The molecules that make up most of the membrane are phospholipids—water-soluble phosphate-containing heads with lipid tails that will do anything to avoid water. Drop a small amount of phospholipids into water, and they will spontaneously form membranes by aligning themselves into double layers, with the water-shy lipid tails sandwiched in the dry area between sheets of the phosphate headgroups. This is just how the membranes in a cell are arranged. The strength of the unfavorable reaction between the tails and water”termed a “hydrophobic effect”—holds the bilayer together with no other bonds.

Along with making up the cellular, or plasma, membrane, such bilayers also hold together many organelles and compartments, such as the DNA-containing nucleus and the energy-producing mitochondria.

Photo: Matthew Septimus

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