Dynamic control of slow water transport by aquaporin 0: implications for hydration and junction stability in the eye lens.
Aquaporin 0 (AQP0), the most abundant membrane protein in mammalian lens fiber cells, not only serves as the primary water channel in this tissue but also appears to mediate the formation of thin junctions between fiber cells. AQP0 is remarkably less water permeable than other aquaporins, but the structural basis and biological significance of this low permeability remain uncertain, as does the permeability of the protein in a reported junctional form. To address these issues, we performed molecular dynamics (MD) simulations of water transport through membrane-embedded AQP0 in both its (octameric) junctional and (tetrameric) nonjunctional forms. From our simulations, we measured an osmotic permeability for the nonjunctional form that agrees with experiment and found that the distinct dynamics of the conserved, lumen-protruding side chains of Tyr-23 and Tyr-149 modulate water passage, accounting for the slow permeation. The junctional and nonjunctional forms conducted water equivalently, in contrast to a previous suggestion based on static crystal structures that water conduction is lost on junction formation. Our analysis suggests that the low water permeability of AQP0 may help maintain the mechanical stability of the junction. We hypothesize that the structural features leading to low permeability may have evolved in part to allow AQP0 to form junctions that both conduct water and contribute to the organizational structure of the fiber cell tissue and microcirculation within it, as required to maintain transparency of the lens.
Jensen
Morten Ø
MØ
D. E. Shaw Research, New York, NY 10036, USA.
Dror
Ron O
RO
Xu
Huafeng
H
Borhani
David W
DW
Arkin
Isaiah T
IT
Eastwood
Michael P
MP
Shaw
David E
DE
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D020346:Aquaporins / Q000737:chemistry* / Q000378:metabolism*; D001692:Biological Transport; D002448:Cell Adhesion; D003198:Computer Simulation; D003459:Crystallins / Q000737:chemistry / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007365:Intercellular Junctions / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D007908:Lens, Crystalline / Q000378:metabolism*; D008958:Models, Molecular; D009995:Osmosis; D017434:Protein Structure, Tertiary; D014867:Water / Q000378:metabolism*
D000596:Amino Acids; D020346:Aquaporins; D003459:Crystallins; D005136:Eye Proteins; C030328:aquaporin 0; D014867:Water
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