Fraser J Moss, Paween Mahinthichaichan, David T Lodowski, Thomas Kowatz, Emad
Tajkhorshid, Andreas Engel, Walter F Boron, and Ardeshir Vahedi-Faridi.
Aquaporin-7: A dynamic aquaglyceroporin with higher water and
glycerol transport capacity than its bacterial homolog GlpF.
Frontiers in Physiology, 11, 2020.
Published.
(PMC: PMC7339978)
MOSS2020-ET
Xenopus oocytes expressing human aquaporin-7 (AQP7) exhibit
greater osmotic water permeability and ^3H-
glycerol uptake vs. those expressing the bacterial glycerol
facilitator GlpF. AQP7-expressing oocytes exposed to
increasing extracellular [glycerol] under isosmolal conditions
exhibit increasing swelling rates, whereas GlpF-
expressing oocytes do not swell at all. To understand these
differences, we performed X-ray crystallography and
molecular-dynamics simulations. The structure reveals AQP7
tetramers containing two monomers with 3 glycerols,
and two monomers with 2 glycerols in the pore. In contrast to
GlpF, no glycerol is bound at the AQP7 selectivity filter
(SF), comprising residues F74, G222, Y223, and R229. The AQP7 SF
is resolved in its closed state because F74
blocks the passage of small solutes. Molecular dynamics
simulations demonstrate that F74 undergoes large and rapid
conformational changes, allowing glycerol molecules to permeate
without orientational restriction. The more rigid
GlpF imposes orientational constraints on glycerol molecules
passing through the SF. Moreover, GlpF-W48
(analogous to AQP7-F74) undergoes rare but long-lasting
conformational changes that block the pore to H_2O and
glycerol.
