Abstract The families
of proteins that transport water, glycerol, ammonia and carbon dioxide
are found across all species. Ammonia transporters and Aquaporins
are highly selective transmembrane channels for permeation of specific
small molecules, with absolute exclusion of ions including protons
or OH- anions and charged solutes, and without dissipating the electrochemical
potential across the cell membrane. The mechanisms of transport are
deduced from structures and assays. The E.coli glycerol facilitator
(GlpF), a water and a glycerol conducting channel structure is determined
at 1.9Å resolution1,2. Subsequently a structure for AQP1 from
erythrocytes followed, and we determined structures for AQP04, AQPZ3,
and AQPM. These channels will be compared to illustrate their function.
A line of hydrogen bonded water molecules are hydrogen bonded to
a line of 8 hydrogen bond acceptors. The first structure of an ammonia
transporter from the Amt/MEP/Rh superfamily, determined to 1.35Å resolution5
shows it to be a channel that spans the membrane 11 times. Two structurally
similar halves span the membrane with opposite polarity. Structures
with and without ammonia, or methyl ammonia show a vestibule that
recruits NH4+/NH3, a binding site for NH4+ and a 20Å long hydrophobic
channel that lowers the NH4+ pKa to below 6 and conducts NH3. Favorable
interactions for NH3 are seen within the channel and use conserved
histidines. Reconstitution of AmtB into vesicles shows that AmtB
conducts uncharged NH3. These are the first structures of gas channels! |