9gsg: Difference between revisions

Latest revision as of 05:35, 6 August 2025

Cryo-EM structure of mouse PMCA-NPTN complex captured in E2-Pi state (ALF4)

Structural highlights

9gsg is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.83Å
Ligands:	ALF, MG, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

AT2B2_MOUSE Defects in Atp2b2 are associated with early onset profound hearing loss and severe vestibular dysfunction.^[1] ^[2]

Function

AT2B2_MOUSE ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems (PubMed:17234811, PubMed:9668038). Uses ATP as an energy source to transport cytosolic Ca(2+) ions across the plasma membrane to the extracellular compartment. Has fast activation and Ca(2+) clearance rate suited to control fast neuronal Ca(2+) dynamics (PubMed:17409239, PubMed:20083513). At parallel fiber to Purkinje neuron synapse, mediates presynaptic Ca(2+) efflux in response to climbing fiber-induced Ca(2+) rise. Provides for fast return of Ca(2+) concentrations back to their resting levels, ultimately contributing to long-term depression induction and motor learning (PubMed:17409239, PubMed:20083513). Plays an essential role in hearing and balance. In cochlear hair cells, shuttles Ca(2+) ions from stereocilia to the endolymph and dissipates Ca(2+) transients generated by the opening of the mechanoelectrical transduction channels. Regulates Ca(2+) levels in the vestibular system, where it contributes to the formation of otoconia (By similarity) (PubMed:9668038). Regulates Ca(2+) signaling through dissipation of Ca(2+) transients generated by store-operated channels (By similarity). In lactating mammary gland, allows for the high content of Ca(2+) ions in the milk (PubMed:15302868).[UniProtKB:Q01814]^[3] ^[4] ^[5] ^[6] ^[7]

References

↑ Ficarella R, Di Leva F, Bortolozzi M, Ortolano S, Donaudy F, Petrillo M, Melchionda S, Lelli A, Domi T, Fedrizzi L, Lim D, Shull GE, Gasparini P, Brini M, Mammano F, Carafoli E. A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness. Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1516-21. PMID:17234811 doi:10.1073/pnas.0609775104
↑ Street VA, McKee-Johnson JW, Fonseca RC, Tempel BL, Noben-Trauth K. Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice. Nat Genet. 1998 Aug;19(4):390-4. PMID:9697703 doi:10.1038/1284
↑ Reinhardt TA, Lippolis JD, Shull GE, Horst RL. Null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2 impairs calcium transport into milk. J Biol Chem. 2004 Oct 8;279(41):42369-73. PMID:15302868 doi:10.1074/jbc.M407788200
↑ Ficarella R, Di Leva F, Bortolozzi M, Ortolano S, Donaudy F, Petrillo M, Melchionda S, Lelli A, Domi T, Fedrizzi L, Lim D, Shull GE, Gasparini P, Brini M, Mammano F, Carafoli E. A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness. Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1516-21. PMID:17234811 doi:10.1073/pnas.0609775104
↑ Empson RM, Garside ML, Knöpfel T. Plasma membrane Ca2+ ATPase 2 contributes to short-term synapse plasticity at the parallel fiber to Purkinje neuron synapse. J Neurosci. 2007 Apr 4;27(14):3753-8. PMID:17409239 doi:10.1523/JNEUROSCI.0069-07.2007
↑ Empson RM, Turner PR, Nagaraja RY, Beesley PW, Knöpfel T. Reduced expression of the Ca(2+) transporter protein PMCA2 slows Ca(2+) dynamics in mouse cerebellar Purkinje neurones and alters the precision of motor coordination. J Physiol. 2010 Mar 15;588(Pt 6):907-22. PMID:20083513 doi:10.1113/jphysiol.2009.182196
↑ Kozel PJ, Friedman RA, Erway LC, Yamoah EN, Liu LH, Riddle T, Duffy JJ, Doetschman T, Miller ML, Cardell EL, Shull GE. Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. J Biol Chem. 1998 Jul 24;273(30):18693-6. PMID:9668038 doi:10.1074/jbc.273.30.18693

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OCA

[1] Ficarella R, Di Leva F, Bortolozzi M, Ortolano S, Donaudy F, Petrillo M, Melchionda S, Lelli A, Domi T, Fedrizzi L, Lim D, Shull GE, Gasparini P, Brini M, Mammano F, Carafoli E. A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness. Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1516-21. PMID:17234811 doi:10.1073/pnas.0609775104

[2] Street VA, McKee-Johnson JW, Fonseca RC, Tempel BL, Noben-Trauth K. Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice. Nat Genet. 1998 Aug;19(4):390-4. PMID:9697703 doi:10.1038/1284

[3] Reinhardt TA, Lippolis JD, Shull GE, Horst RL. Null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2 impairs calcium transport into milk. J Biol Chem. 2004 Oct 8;279(41):42369-73. PMID:15302868 doi:10.1074/jbc.M407788200

[4] Ficarella R, Di Leva F, Bortolozzi M, Ortolano S, Donaudy F, Petrillo M, Melchionda S, Lelli A, Domi T, Fedrizzi L, Lim D, Shull GE, Gasparini P, Brini M, Mammano F, Carafoli E. A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness. Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1516-21. PMID:17234811 doi:10.1073/pnas.0609775104

[5] Empson RM, Garside ML, Knöpfel T. Plasma membrane Ca2+ ATPase 2 contributes to short-term synapse plasticity at the parallel fiber to Purkinje neuron synapse. J Neurosci. 2007 Apr 4;27(14):3753-8. PMID:17409239 doi:10.1523/JNEUROSCI.0069-07.2007

[6] Empson RM, Turner PR, Nagaraja RY, Beesley PW, Knöpfel T. Reduced expression of the Ca(2+) transporter protein PMCA2 slows Ca(2+) dynamics in mouse cerebellar Purkinje neurones and alters the precision of motor coordination. J Physiol. 2010 Mar 15;588(Pt 6):907-22. PMID:20083513 doi:10.1113/jphysiol.2009.182196

[7] Kozel PJ, Friedman RA, Erway LC, Yamoah EN, Liu LH, Riddle T, Duffy JJ, Doetschman T, Miller ML, Cardell EL, Shull GE. Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. J Biol Chem. 1998 Jul 24;273(30):18693-6. PMID:9668038 doi:10.1074/jbc.273.30.18693

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9gsg is ON HOLD  until Paper Publication
+==Cryo-EM structure of mouse PMCA-NPTN complex captured in E2-Pi state (ALF4)==
+<StructureSection load='9gsg' size='340' side='right'caption='[[9gsg]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
-Authors: Vinayagam, D., Raunser, S., Sistel, O., Schulte, U., Constantin, C.E., Prumbaum, D., Zolles, G., Fakler, B.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9gsg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9GSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9GSG FirstGlance]. <br>
-Description: Cryo-EM structure of mouse PMCA-NPTN complex captured in E2-Pi state (ALF4)
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.83&#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=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-[[Category: Schulte, U]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9gsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9gsg OCA], [https://pdbe.org/9gsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9gsg RCSB], [https://www.ebi.ac.uk/pdbsum/9gsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9gsg ProSAT]</span></td></tr>
-[[Category: Vinayagam, D]]
+</table>
-[[Category: Fakler, B]]
+== Disease ==
-[[Category: Sistel, O]]
+[https://www.uniprot.org/uniprot/AT2B2_MOUSE AT2B2_MOUSE] Defects in Atp2b2 are associated with early onset profound hearing loss and severe vestibular dysfunction.<ref>PMID:17234811</ref> <ref>PMID:9697703</ref>
-[[Category: Prumbaum, D]]
+== Function ==
-[[Category: Raunser, S]]
+[https://www.uniprot.org/uniprot/AT2B2_MOUSE AT2B2_MOUSE] ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems (PubMed:17234811, PubMed:9668038). Uses ATP as an energy source to transport cytosolic Ca(2+) ions across the plasma membrane to the extracellular compartment. Has fast activation and Ca(2+) clearance rate suited to control fast neuronal Ca(2+) dynamics (PubMed:17409239, PubMed:20083513). At parallel fiber to Purkinje neuron synapse, mediates presynaptic Ca(2+) efflux in response to climbing fiber-induced Ca(2+) rise. Provides for fast return of Ca(2+) concentrations back to their resting levels, ultimately contributing to long-term depression induction and motor learning (PubMed:17409239, PubMed:20083513). Plays an essential role in hearing and balance. In cochlear hair cells, shuttles Ca(2+) ions from stereocilia to the endolymph and dissipates Ca(2+) transients generated by the opening of the mechanoelectrical transduction channels. Regulates Ca(2+) levels in the vestibular system, where it contributes to the formation of otoconia (By similarity) (PubMed:9668038). Regulates Ca(2+) signaling through dissipation of Ca(2+) transients generated by store-operated channels (By similarity). In lactating mammary gland, allows for the high content of Ca(2+) ions in the milk (PubMed:15302868).[UniProtKB:Q01814]<ref>PMID:15302868</ref> <ref>PMID:17234811</ref> <ref>PMID:17409239</ref> <ref>PMID:20083513</ref> <ref>PMID:9668038</ref>
-[[Category: Zolles, G]]
+== References ==
-[[Category: Constantin, C.E]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Constantin CE]]
+[[Category: Fakler B]]
+[[Category: Prumbaum D]]
+[[Category: Raunser S]]
+[[Category: Schulte U]]
+[[Category: Sistel O]]
+[[Category: Vinayagam D]]
+[[Category: Zolles G]]

9gsg: Difference between revisions

Latest revision as of 05:35, 6 August 2025

Cryo-EM structure of mouse PMCA-NPTN complex captured in E2-Pi state (ALF4)

Structural highlights

Disease

Function

References

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