Mechanism of aquaporin-4's fast and highly selective water conduction and proton exclusion.
Members of the aquaporin (AQP) family are expressed in almost every organism, including 13 homologues in humans. Based on the electron crystallographic structure of AQP1, the hydrogen-bond isolation mechanism was proposed to explain why AQPs are impermeable to protons despite their very fast water conduction. The mechanism by which AQPs exclude protons remained controversial, however. Here we present the structure of AQP4 at 2.8 A resolution obtained by electron crystallography of double-layered two-dimensional crystals. The resolution has been improved from the previous 3.2 A, with accompanying improvement in data quality resulting in the ability to identify individual water molecules. Our structure of AQP4, the predominant water channel in the brain, reveals eight water molecules in the channel. The arrangement of the waters provides support for the hydrogen-bond isolation mechanism. Our AQP4 structure also visualizes five lipids, showing that direct interactions of the extracellular surface of AQP4 with three lipids in the adjoining membrane help stabilize the membrane junction.
Tani
Kazutoshi
K
Department of Biophysics, Faculty of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
Mitsuma
Tadanori
T
Hiroaki
Yoko
Y
Kamegawa
Akiko
A
Nishikawa
Kouki
K
Tanimura
Yukihiro
Y
Fujiyoshi
Yoshinori
Y
D000818:Animals; D051401:Aquaporin 4 / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D011522:Protons; D051381:Rats; D014867:Water / Q000737:chemistry*
D051401:Aquaporin 4; D008055:Lipids; D011522:Protons; D014867:Water