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Article Abstract
Ion-transport mechanisms evolve by changing ion-selectivity, such as switching from Na to H selectivity in secondary-active transporters or P-type-ATPases. Here we study primary-active transport via P-type ATPases using functional and structural analyses to demonstrate that four simultaneous residue substitutions transform the non-gastric H/K pump, a strict H-dependent electroneutral P-type ATPase, into a bona fide Na-dependent electrogenic Na/K pump. Conversion of a H-dependent primary-active transporter into a Na-dependent one provides a prototype for similar studies of ion-transport proteins. Moreover, we solve the structures of the wild-type non-gastric H/K pump, a suitable drug target to treat cystic fibrosis, and of its Na/K pump-mimicking mutant in two major conformations, providing insight on how Na binding drives a concerted mechanism leading to Na/K pump phosphorylation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463140 | PMC |
| http://dx.doi.org/10.1038/s41467-022-32793-0 | DOI Listing |
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