Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.25.266742v1?rss=1

Authors: Li, H., Bai, L., You, Q., Jain, B. K., Graham, T. R., Kovach, A.

Abstract:

The P4 ATPases are a family of membrane enzymes that transport lipids across membrane bilayers. The structures of the class-1 phosphatidylserine flippases have been reported, revealing a substrate site on lumenal side. However, the cytosolic binding site has not been found, and the transport mechanisms of P4 ATPases in other classes are unknown. Here we report a structural and functional study on plasma-membrane localized, class-3 P4 ATPases Dnf1-Lem3 and Dnf2-Lem3. We captured substrate lipids on both the exoplasmic and cytosolic sides, and found that these two enzymes have similar structures. We found a helix-turn-helix motif in the cytosolic P domain that is unique to the class-3 enzymes and plays a crucial role in their function. Unexpectedly, Lem3 contributes to substrate binding near the cytosolic surface. Conformational transitions of these two class-3 enzymes match those of the class-1 enzymes, suggesting a conserved mechanism among all classes of P4 ATPases.

Copy rights belong to original authors. Visit the link for more info