Jin Yu, Andrea J. Yool, Klaus Schulten, and Emad Tajkhorshid.
Mechanism of gating and ion conductivity of a possible tetrameric
pore in Aquaporin-1.
Structure, 14:1411-1423, 2006.
YU2006
While substrate permeation through monomeric pores of aquaporins is well characterized,
little is known about the possible tetrameric pore. AQP1 has been suggested to function as
an ion channel upon cGMP activation, although this idea has been controversial. Taking a
theoretical and experimental approach, we demonstrate that the current might arise through
the tetrameric pore and propose a plausible mechanism for conduction and gating. In response
to simulated ion permeation, immediate hydration of the putative central pore was
facilitated by moderate conformational changes of pore-lining residues. cGMP is found to
interact with an unusually arginine-rich, cytoplasmic loop (loop D) facilitating its outward
motion, which is hypothesized to trigger the opening of a cytoplasmic gate. Physiological
analyses of wild type AQP1 and a designed mutant in which two arginines of the gating loop
are replaced by alanine provide experimental support for identifying a key component of the
proposed mechanism.
