The structure of AQP1 water channel was determined to 2.2 Å resolution. The channel consists of three topological elements, an extracellular and a cytoplasmic vestibule connected by an extended narrow pore or selectivity filter. At the extracellular end of the selectivity filter is the constriction region, which establishes the steric upper limit of the channel and has an effective solvent accessible diameter of ~2.8 Å. Within the selectivity filter, four bound waters are localized along three hydrophilic nodes which punctuate an otherwise extremely hydrophobic pore segment. This novel combination of a long hydrophobic pore and a minimal number of solute binding sites facilitates rapid water transport. Residues of the constriction region, in particular histidine 182 which is conserved among all known water specific channels, are critical in establishing water specificity. Analysis of the AQP1 pore also indicates that the transport of protons through this channel is highly energetically unfavorable.

Summary The diverse functions of microtubules require stiff structures possessing sufficient lateral flexibility to enable bending with high curvature. We used cryo-electron microscopy to investigate the molecular basis for these critical mechanical properties. High-quality structural maps were used to build pseudo-atomic models of microtubules containing 11 to 16 protofilaments, representing a wide range of lateral curvature. Protofilaments in all these microtubules were connected primarily via inter-protofilament interactions between the M loops, and the H1′-S2 and H2-S3 loops. We postulate that the tolerance of the loop-loop interactions to lateral deformation provides the capacity for high-curvature bending without breaking. On the other hand, the local molecular architecture that surrounds these connecting loops contributes to the overall rigidity. Inter-protofilament interactions in the seam region are similar to those in the normal helical regions, suggesting that the existence of the seam does not significantly affect the mechanical properties of microtubules.