Panel A shows a three dimensional protein structure, illustrating the human AQP12 tetramer with labeled pore residues. Panel B shows a three dimensional protein structure, depicting a human AQP12 monomer in membrane view with pore residues. Panel C shows a three dimensional protein structure, illustrating the human AQP12 trimer with labeled pore residues. Panel D shows a three dimensional protein structure, depicting the human AQP12 monomer highlighting the proposed pore closure mechanism. Panel E shows a three dimensional protein structure, illustrating the zebrafish Aqp12 tetramer with labeled pore residues. Panel F shows a three dimensional protein structure, depicting a zebrafish Aqp12 monomer in membrane view with pore residues. Panel G shows a three dimensional protein structure, illustrating the zebrafish Aqp12 trimer with labeled pore residues. Panel H shows a three dimensional protein structure, depicting the zebrafish Aqp12 monomer highlighting the proposed pore closure mechanism.
Quaternary and tertiary in silico structures of human and zebrafish AQP12. (A, C, E , and G ) Cartoon renders of HsAQP12A and DrAqp12 putative tetramers and trimers showing the monomeric pores 1–4 and 1–3, respectively. The tetramers are modeled on GlpF templates (8Y8W, 8Y8X) and the trimers on an AQP11 template (9VXW). In each render, loop E holds the second hemihelix (magenta) and the ar/R residues Leu203 and Leu208 (spacefill, green) for HsAQP12 and DrAqp12, respectively. The mercury-sensitive HsAQP12 Cys211 and DrAqp12 Cys216 residues (spacefill, yellow) are located at the end of the second hemihelix. The inactive HsAQP12 Cys139 and DrAqp12 Cys144 residues (spacefill, cyan) reside in loop C (cyan). In the trimer, the inactive and mercury-sensitive Cys residues form a disulfide bridge between loop C and loop E, respectively. (B, D, F, and H) Membrane planar views of HsAQP12 and DrAqp12 monomers showing the second hemihelix, Cys, and ar/R residues labeled as in A, C, D, and E. The amino and carboxy termini are labeled NT and CT, respectively. Red arrows indicate the potential basis for pore closure through rotation or collapse of the second hemihelix when mercury binds to the sensitive Cys residues.