Fig. 6: A proposed model of hATP13A2 transporting polyamines.
From: Conformational cycle of human polyamine transporter ATP13A2
During the E1-to-E1P transition, ATP binding induces the A, P, and N domains to tight together, producing a catalytic center. In E2P state, conformational rearrangements in the cytosolic domains and transmembrane regions induce the opening of the entrance pocket Site1, and the negatively charged amino acids are enabled to recruit positively charged polyamines (shown in green). The Site1 captured polyamines will then move to the inward-open cavity formed by Site2 in the E2-Pi state, resulting in an increasing concentration of polyamines in the buffering tank (shown in brown). Finally, polyamines will diffuse into the cytoplasm through the cleft between TM2 and TM4b in the E2 state. The lipids (shown in purple) attached to the exit might accelerate the release of polyamine into the cytoplasm.
