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7x20

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Crystal structure of non gastric H,K-ATPase alpha2 in (K+)E2-AlF state

Structural highlights

7x20 is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.3Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AT12A_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 PubMed

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.

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.

References

↑ Sangan P, Thevananther S, Sangan S, Rajendran VM, Binder HJ. Colonic H-K-ATPase alpha- and beta-subunits express ouabain-insensitive H-K-ATPase. Am J Physiol Cell Physiol. 2000 Jan;278(1):C182-9. doi:, 10.1152/ajpcell.2000.278.1.C182. PMID:10644526 doi:http://dx.doi.org/10.1152/ajpcell.2000.278.1.C182
↑ Lee J, Rajendran VM, Mann AS, Kashgarian M, Binder HJ. Functional expression and segmental localization of rat colonic K-adenosine triphosphatase. J Clin Invest. 1995 Oct;96(4):2002-8. doi: 10.1172/JCI118247. PMID:7560093 doi:http://dx.doi.org/10.1172/JCI118247
↑ Young VC, Nakanishi H, Meyer DJ, Nishizawa T, Oshima A, Artigas P, Abe K. Structure and function of H(+)/K(+) pump mutants reveal Na(+)/K(+) pump mechanisms. Nat Commun. 2022 Sep 9;13(1):5270. doi: 10.1038/s41467-022-32793-0. PMID:36085139 doi:http://dx.doi.org/10.1038/s41467-022-32793-0