8d3x

Human alpha3 Na+/K+-ATPase in its K+-occluded stateHuman alpha3 Na+/K+-ATPase in its K+-occluded state

Structural highlights

8d3x is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.1Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AT1B1_HUMAN This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane (PubMed:19694409). Plays a role in innate immunity by enhancing virus-triggered induction of interferons (IFNs) and interferon stimulated genes (ISGs). Mechanistically, enhances the ubiquitination of TRAF3 and TRAF6 as well as the phosphorylation of TAK1 and TBK1 (PubMed:34011520).^[1] ^[2] Involved in cell adhesion and establishing epithelial cell polarity.^[3]

Publication Abstract from PubMed

P2-type ATPase sodium-potassium pumps (Na(+)/K(+)-ATPases) are ion-transporting enzymes that use ATP to transport Na(+) and K(+) on opposite sides of the lipid bilayer against their electrochemical gradients to maintain ion concentration gradients across the membranes in all animal cells. Despite the available molecular architecture of the Na(+)/K(+)-ATPases, a complete molecular mechanism by which the Na(+) and K(+) ions access into and are released from the pump remains unknown. Here we report five cryo-electron microscopy (cryo-EM) structures of the human alpha3 Na(+)/K(+)-ATPase in its cytoplasmic side-open (E1), ATP-bound cytoplasmic side-open (E1*ATP), ADP-AlF(4)(-) trapped Na(+)-occluded (E1*P-ADP), BeF(3)(-) trapped exoplasmic side-open (E2P) and MgF(4)(2-) trapped K(+)-occluded (E2*P(i)) states. Our work reveals the atomically resolved structural detail of the cytoplasmic gating mechanism of the Na(+)/K(+)-ATPase.

Structural basis for gating mechanism of the human sodium-potassium pump.,Nguyen PT, Deisl C, Fine M, Tippetts TS, Uchikawa E, Bai XC, Levine B Nat Commun. 2022 Sep 8;13(1):5293. doi: 10.1038/s41467-022-32990-x. PMID:36075933^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bab-Dinitz E, Albeck S, Peleg Y, Brumfeld V, Gottschalk KE, Karlish SJ. A C-terminal lobe of the beta subunit of Na,K-ATPase and H,K-ATPase resembles cell adhesion molecules. Biochemistry. 2009 Sep 15;48(36):8684-91. doi: 10.1021/bi900868e. PMID:19694409 doi:http://dx.doi.org/10.1021/bi900868e
↑ Cao W, Guo Y, Cheng Z, Xu G, Zuo Q, Nie L, Huang Y, Liu S, Zhu Y. Inducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the Ubiquitination of TRAF3 and TRAF6. J Immunol. 2021 Jun 1;206(11):2668-2681. doi: 10.4049/jimmunol.2001262. Epub 2021, May 19. PMID:34011520 doi:http://dx.doi.org/10.4049/jimmunol.2001262
↑ Bab-Dinitz E, Albeck S, Peleg Y, Brumfeld V, Gottschalk KE, Karlish SJ. A C-terminal lobe of the beta subunit of Na,K-ATPase and H,K-ATPase resembles cell adhesion molecules. Biochemistry. 2009 Sep 15;48(36):8684-91. doi: 10.1021/bi900868e. PMID:19694409 doi:http://dx.doi.org/10.1021/bi900868e
↑ Nguyen PT, Deisl C, Fine M, Tippetts TS, Uchikawa E, Bai XC, Levine B. Structural basis for gating mechanism of the human sodium-potassium pump. Nat Commun. 2022 Sep 8;13(1):5293. doi: 10.1038/s41467-022-32990-x. PMID:36075933 doi:http://dx.doi.org/10.1038/s41467-022-32990-x

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OCA

[1] Bab-Dinitz E, Albeck S, Peleg Y, Brumfeld V, Gottschalk KE, Karlish SJ. A C-terminal lobe of the beta subunit of Na,K-ATPase and H,K-ATPase resembles cell adhesion molecules. Biochemistry. 2009 Sep 15;48(36):8684-91. doi: 10.1021/bi900868e. PMID:19694409 doi:http://dx.doi.org/10.1021/bi900868e

[2] Cao W, Guo Y, Cheng Z, Xu G, Zuo Q, Nie L, Huang Y, Liu S, Zhu Y. Inducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the Ubiquitination of TRAF3 and TRAF6. J Immunol. 2021 Jun 1;206(11):2668-2681. doi: 10.4049/jimmunol.2001262. Epub 2021, May 19. PMID:34011520 doi:http://dx.doi.org/10.4049/jimmunol.2001262

[3] Bab-Dinitz E, Albeck S, Peleg Y, Brumfeld V, Gottschalk KE, Karlish SJ. A C-terminal lobe of the beta subunit of Na,K-ATPase and H,K-ATPase resembles cell adhesion molecules. Biochemistry. 2009 Sep 15;48(36):8684-91. doi: 10.1021/bi900868e. PMID:19694409 doi:http://dx.doi.org/10.1021/bi900868e

[4] Nguyen PT, Deisl C, Fine M, Tippetts TS, Uchikawa E, Bai XC, Levine B. Structural basis for gating mechanism of the human sodium-potassium pump. Nat Commun. 2022 Sep 8;13(1):5293. doi: 10.1038/s41467-022-32990-x. PMID:36075933 doi:http://dx.doi.org/10.1038/s41467-022-32990-x

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