9ovr: Difference between revisions

Latest revision as of 10:46, 3 September 2025

CryoEM structural insight into the breast cancer pH regulator NBCn1

Structural highlights

9ovr is a 2 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 3.3Å
Ligands:	CO3, NA, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

S4A7_HUMAN Electroneutral sodium- and bicarbonate-dependent cotransporter with a Na(+):HCO3(-) 1:1 stoichiometry (PubMed:10347222, PubMed:12403779, PubMed:14578046, PubMed:14736710). Mediates the sodium-dependent bicarbonate transport important for pH recovery after acid load as well as for regulation of steady-state pH in the duodenum and vascular smooth muscle cells (By similarity). Plays a key role in macrophage acidification, mediating bicarbonate import into the cytoplasm which is crucial for net acid extrusion and maintenance of cytoplasmic pH during phagocytosis (PubMed:29779931). Provides cellular bicarbonate for de novo purine and pyrimidine synthesis and is a key mediator of de novo nucleotide synthesis downstream of mTORC1 signaling in proliferating cells (PubMed:35772404).[UniProtKB:Q8BTY2]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] Plays a key role in macrophage acidification, mediating bicarbonate import into the cytoplasm which is crucial for net acid extrusion and maintenance of cytoplasmic pH during phagocytosis.^[7]

References

↑ Pushkin A, Abuladze N, Lee I, Newman D, Hwang J, Kurtz I. Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family. J Biol Chem. 1999 Jun 4;274(23):16569-75. PMID:10347222 doi:10.1074/jbc.274.23.16569
↑ Park M, Ko SB, Choi JY, Muallem G, Thomas PJ, Pushkin A, Lee MS, Kim JY, Lee MG, Muallem S, Kurtz I. The cystic fibrosis transmembrane conductance regulator interacts with and J Biol Chem. 2002 Dec 27;277(52):50503-9. PMID:12403779 doi:10.1074/jbc.M201862200
↑ Loiselle FB, Jaschke P, Casey JR. Structural and functional characterization of the human NBC3 sodium/bicarbonate co-transporter carboxyl-terminal cytoplasmic domain. Mol Membr Biol. 2003 Oct-Dec;20(4):307-17. PMID:14578046 doi:10.1080/0968768031000122520
↑ Loiselle FB, Morgan PE, Alvarez BV, Casey JR. Regulation of the human NBC3 Na+/HCO3 PKA. Am J Physiol Cell Physiol. 2004 Jun;286(6):C1423-33. PMID:14736710 doi:10.1152/ajpcell.00382.2003
↑ Sedlyarov V, Eichner R, Girardi E, Essletzbichler P, Goldmann U, Nunes-Hasler P, Srndic I, Moskovskich A, Heinz LX, Kartnig F, Bigenzahn JW, Rebsamen M, Kovarik P, Demaurex N, Superti-Furga G. The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. Cell Host Microbe. 2018 Jun 13;23(6):766-774.e5. PMID:29779931 doi:10.1016/j.chom.2018.04.013
↑ Ali ES, Lipońska A, O'Hara BP, Amici DR, Torno MD, Gao P, Asara JM, Yap MF, Mendillo ML, Ben-Sahra I. The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis. Mol Cell. 2022 Sep 1;82(17):3284-3298.e7. PMID:35772404 doi:10.1016/j.molcel.2022.06.008
↑ Sedlyarov V, Eichner R, Girardi E, Essletzbichler P, Goldmann U, Nunes-Hasler P, Srndic I, Moskovskich A, Heinz LX, Kartnig F, Bigenzahn JW, Rebsamen M, Kovarik P, Demaurex N, Superti-Furga G. The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. Cell Host Microbe. 2018 Jun 13;23(6):766-774.e5. PMID:29779931 doi:10.1016/j.chom.2018.04.013

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OCA

[1] Pushkin A, Abuladze N, Lee I, Newman D, Hwang J, Kurtz I. Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family. J Biol Chem. 1999 Jun 4;274(23):16569-75. PMID:10347222 doi:10.1074/jbc.274.23.16569

[2] Park M, Ko SB, Choi JY, Muallem G, Thomas PJ, Pushkin A, Lee MS, Kim JY, Lee MG, Muallem S, Kurtz I. The cystic fibrosis transmembrane conductance regulator interacts with and J Biol Chem. 2002 Dec 27;277(52):50503-9. PMID:12403779 doi:10.1074/jbc.M201862200

[3] Loiselle FB, Jaschke P, Casey JR. Structural and functional characterization of the human NBC3 sodium/bicarbonate co-transporter carboxyl-terminal cytoplasmic domain. Mol Membr Biol. 2003 Oct-Dec;20(4):307-17. PMID:14578046 doi:10.1080/0968768031000122520

[4] Loiselle FB, Morgan PE, Alvarez BV, Casey JR. Regulation of the human NBC3 Na+/HCO3 PKA. Am J Physiol Cell Physiol. 2004 Jun;286(6):C1423-33. PMID:14736710 doi:10.1152/ajpcell.00382.2003

[5] Sedlyarov V, Eichner R, Girardi E, Essletzbichler P, Goldmann U, Nunes-Hasler P, Srndic I, Moskovskich A, Heinz LX, Kartnig F, Bigenzahn JW, Rebsamen M, Kovarik P, Demaurex N, Superti-Furga G. The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. Cell Host Microbe. 2018 Jun 13;23(6):766-774.e5. PMID:29779931 doi:10.1016/j.chom.2018.04.013

[6] Ali ES, Lipońska A, O'Hara BP, Amici DR, Torno MD, Gao P, Asara JM, Yap MF, Mendillo ML, Ben-Sahra I. The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis. Mol Cell. 2022 Sep 1;82(17):3284-3298.e7. PMID:35772404 doi:10.1016/j.molcel.2022.06.008

[7] Sedlyarov V, Eichner R, Girardi E, Essletzbichler P, Goldmann U, Nunes-Hasler P, Srndic I, Moskovskich A, Heinz LX, Kartnig F, Bigenzahn JW, Rebsamen M, Kovarik P, Demaurex N, Superti-Furga G. The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. Cell Host Microbe. 2018 Jun 13;23(6):766-774.e5. PMID:29779931 doi:10.1016/j.chom.2018.04.013

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9ovr is ON HOLD  until Paper Publication
+==CryoEM structural insight into the breast cancer pH regulator NBCn1==
+<StructureSection load='9ovr' size='340' side='right'caption='[[9ovr]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9ovr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9OVR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9OVR FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9ovr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ovr OCA], [https://pdbe.org/9ovr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ovr RCSB], [https://www.ebi.ac.uk/pdbsum/9ovr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ovr ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/S4A7_HUMAN S4A7_HUMAN] Electroneutral sodium- and bicarbonate-dependent cotransporter with a Na(+):HCO3(-) 1:1 stoichiometry (PubMed:10347222, PubMed:12403779, PubMed:14578046, PubMed:14736710). Mediates the sodium-dependent bicarbonate transport important for pH recovery after acid load as well as for regulation of steady-state pH in the duodenum and vascular smooth muscle cells (By similarity). Plays a key role in macrophage acidification, mediating bicarbonate import into the cytoplasm which is crucial for net acid extrusion and maintenance of cytoplasmic pH during phagocytosis (PubMed:29779931). Provides cellular bicarbonate for de novo purine and pyrimidine synthesis and is a key mediator of de novo nucleotide synthesis downstream of mTORC1 signaling in proliferating cells (PubMed:35772404).[UniProtKB:Q8BTY2]<ref>PMID:10347222</ref> <ref>PMID:12403779</ref> <ref>PMID:14578046</ref> <ref>PMID:14736710</ref> <ref>PMID:29779931</ref> <ref>PMID:35772404</ref>   Plays a key role in macrophage acidification, mediating bicarbonate import into the cytoplasm which is crucial for net acid extrusion and maintenance of cytoplasmic pH during phagocytosis.<ref>PMID:29779931</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Alexander P]]
+[[Category: Hong Z]]
+[[Category: Hristina RZ]]
+[[Category: Ira K]]
+[[Category: Kirill T]]
+[[Category: Weiguang W]]

9ovr: Difference between revisions

Latest revision as of 10:46, 3 September 2025

CryoEM structural insight into the breast cancer pH regulator NBCn1

Structural highlights

Function

References

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