Like an opera house, which has its public entrance separate from that for the performers, a cell has different doors for different molecules. Each gets scrutinized at its door before it can enter the cell. Now researchers from the University of California at San Francisco have revealed in the journal Science the three-dimensional structure of one such door, or membrane channel, that specializes in granting entry to a membrane component known as glycerol. Specifically the channel is called the glycerol facilitator (GlpF), from the bacterium Escherichia coli.
Bearing three alcohol groups, glycerol is a basic building block for the cell membrane. (Other components include fatty acids and small charged molecules.) And not just in E. coli. Indeed, although the channel the researchers studied is from a bacterium, it belongs to a large protein family dubbed the aquaporins, which are found in species ranging from bacteria to humans. In fact, a mutation in one of the human versions, called AQP2, causes a certain type of diabetes.
GlpF is highly specific for glycerol and similar polyalcohols. Somehow, even though water molecules are much smaller, they cannot enter. The new study reveals why. In order for glycerol to clear the four-channel configuration in the cell membrane, it must pass through a narrow selectivity filter in the center of a channel. Here it is surrrounded by amino acids that closely match its own structure, which is hydrophilic ("water-loving") on one side and hydrophobic ("water-fearing") on the other. Water molecules, in contrast, can only pass through this area in single file, which is not energetically favorable, because they like to bond to one another. And ions, which are charged, are unable to pass the "water-fearing" side of the channel. This cell entrance, it seems, is truly exclusive.