7x23
From Proteopedia
Cryo-EM structure of non gastric H,K-ATPase alpha2 SPWC mutant in 3Na+E1-AMPPCPF state
Structural highlights
FunctionAT12A_RAT The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+) ATPase pump which transports K(+) ions in exchange for Na(+) and/or H(+) ions across the apical membrane of epithelial cells. Uses ATP as an energy source to pump K(+) ions into the cell while transporting Na(+) and/or H(+) ions to the extracellular compartment (PubMed:10644526, PubMed:7560093). Involved in the maintenance of electrolyte homeostasis through K(+) ion absorption in kidney and colon (By similarity). In the airway epithelium, may play a primary role in mucus acidification regulating its viscosity and clearance (By similarity).[UniProtKB:P54707][UniProtKB:Q9Z1W8][1] [2] Publication Abstract from PubMedIon-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. Structure and function of H(+)/K(+) pump mutants reveal Na(+)/K(+) pump mechanisms.,Young VC, Nakanishi H, Meyer DJ, Nishizawa T, Oshima A, Artigas P, Abe K Nat Commun. 2022 Sep 9;13(1):5270. doi: 10.1038/s41467-022-32793-0. PMID:36085139[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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