This year, Roderick MacKinnon was recognized for working out the atomic structure of an ion channel and Peter Agre for discovering that a major protein found in red blood cells functions primarily as a water channel. Agre went on to establish the family of related channels, which he named "aquaporins." Solving the structure of these channels provided a platform for exploring the underlying molecular mechanisms that allow the proteins to function as filters and maintain osmotic equilibrium. Robert Stroud and colleagues, as reported in this issue of PLoS Biology, have now solved the structure of the water channel from Escherichia coli called aquaporin Z. This channel is especially interesting in that it selectively conducts only water at high rates.
Aquaporins form a large, diverse family of proteins and have been found in bacteria, plants, and animals. Less than a decade ago, scientists discovered the aquaporin Z gene (aqpZ) in E. coli, pointing to the protein's role in regulating water transport in this prokaryote. The aquaporin Z channel protein in E. coli can accommodate a flow of water at rates six times higher than GlpF (aquaglyceroporin glycerol facilitator, a channel protein that transports both glycerol and water in E. coli) making it the prime subject for studying the selectivity of a high-conducting water channel. And because the two main classes of aquaporins occur in E. coli--which means they're exposed to the same cellular environment--the opportunities for comparative structural and functional analyses, combined with site-directed mutagenesis, promise to provide valuable insights into the molecular underpinnings of the selectivity of functionally different aquaporins.
After producing a recombinant form of AqpZ in E. coli, the proteins were crystallized--capturing five water molecules inside--and then analyzed by state-of-the-art high-resolution X-ray diffraction techniques. The architecture of aquaporin Z is typical of aquaporins, with a spiral of eight oxygens providing water-binding sites inside the channel. The outer membrane and cytoplasmic ends of the channel are wider than the interior, which is long and narrow. This structure demonstrates that aquaporin selectivity arises in part from erecting a physical barrier: small molecules, like water, can easily pass, but larger ones simply can't fit. And the strategic positioning of amino acid residues with hydrophilic or hydrophobic properties along the channel helps police the influx of molecules based on their affinity for water. While it seems two amino acid chains located in the middle of the channel also provide a water-friendly surface, Stroud et al. say they play a more intriguing role. Noting that the water molecules occupy the channel in single file, the scientists explain that such an orientation would normally facilitate the random flow of protons (or hydrogen ions), which would be lethal to the cell. This central amino acid pair, they say, restricts the behavior of water molecules in the center of the channel in such a way that prevents "proton jumping" yet keeps the water flowing. With two structural models of aquaporins down to the atomic level in the same species, scientists can now begin to investigate the molecular mechanisms that facilitate their selectivity. The importance of understanding these widely distributed channel proteins was underscored by the Nobel awards this year.
The above post is reprinted from materials provided by Public Library Of Science. Note: Materials may be edited for content and length.
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