Water, water, everywhere...

Tonicity-responsive enhancer binding protein (TonEBP or nuclear factor of activated T cells 5 (NFAT5)) is the only mammalian transcription factor known to regulate gene expression in response to hypertonicity. Unlike other members of the NFAT transcription-factor family, TonEBP acts as a homodimer and binds asymmetric TonE sites with a low affinity. It has been unclear how TonEBP binds these sites, but Chen and colleagues have now determined the 2.86 Å crystal structure of TonEBP complexed with DNA.

Each monomer of TonEBP has amino- and carboxy-terminal immunoglobulin-like domains that extend away from one another. In the homodimer, there are two interfaces. One ? which is similar to that seen for nuclear factor (NF)-κB dimers ? is between the carboxy-terminal domains, and the other ? which is similar to the surface that NFAT uses to contact Fos?Jun ? is between the amino-terminal domains. This homodimer forms a complete circle around the DNA, with DNA bound to one side.

The authors showed that this DNA encirclement probably increases the kinetic stability of TonEBP?DNA complexes, which helps to override TonEBP's low DNA-binding affinity. This work has added a sequence-specific transcription factor to the list of factors that bind DNA by encirclement, and has also revealed that the NFAT and NF-κB transcription factor families might be more closely related than was previously thought. REFERENCEStroud, J. C. et al. Structure of a TonEBP?DNA complex reveals DNA encircled by a transcription factor. Nature Struct. Biol. (2002) Jan 7; [article]

...for aquaporins to 'drink'

Reprinted by permission from Nature 414, 872?878 © (2001) Macmillan Magazines Ltd.

Aquaporins (AQPs) transport water across cell membranes in response to osmotic gradients. AQP1 allows water ? but not ions (including protons) ? to move freely and reversibly across cell membranes, but it is not clear how this water moves or how this specificity is achieved. Clearer insights have now been provided by Jap and co-workers, who have solved the crystal structure of bovine AQP1 to 2.2 Å resolution.

AQP1 functions as a tetramer, where each monomer has its own water channel. Each channel comprises an extracellular and cytoplasmic 'vestibule', connected by an extended narrow pore. In the crystal structure, only four bound water molecules interrupt this hydrophobic pore at three hydrophilic nodes, an arrangement that facilitates rapid water transport. The authors conclude that the transport of protons through this pore is probably energetically unfavourable, because of the lack of a hydrogen-bonded network of water molecules through which protons could 'shuttle'. They also found that residues of the constriction region ? the narrowest point of the pore ? are critical for conferring water specificity. REFERENCESui, H. et al. Structural basis of water-specific transport through the AQP1 water channel. Nature 414, 872?878 (2001) PubMed