8fhh

From Proteopedia

(Difference between revisions)

Current revision

Wildtype rabbit TRPV5 in nanodiscs in the presence of oleoyl coenzyme A, Closed stated

Structural highlights

8fhh is a 4 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.09Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRPV5_RABIT Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12574114). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).[UniProtKB:P69744][UniProtKB:Q9NQA5]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Long-chain acyl-coenzyme A (LC-CoA) is a crucial metabolic intermediate that plays important cellular regulatory roles, including activation and inhibition of ion channels. The structural basis of ion channel regulation by LC-CoA is not known. Transient receptor potential vanilloid 5 and 6 (TRPV5 and TRPV6) are epithelial calcium-selective ion channels. Here, we demonstrate that LC-CoA activates TRPV5 and TRPV6 in inside-out patches, and both exogenously supplied and endogenously produced LC-CoA can substitute for the natural ligand phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) in maintaining channel activity in intact cells. Utilizing cryo-electron microscopy, we determined the structure of LC-CoA-bound TRPV5, revealing an open configuration with LC-CoA occupying the same binding site as PI(4,5)P(2) in previous studies. This is consistent with our finding that PI(4,5)P(2) could not further activate the channels in the presence of LC-CoA. Our data provide molecular insights into ion channel regulation by a metabolic signaling molecule.

Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A.,Lee BH, De Jesus Perez JJ, Moiseenkova-Bell V, Rohacs T Nat Commun. 2023 Sep 21;14(1):5883. doi: 10.1038/s41467-023-41577-z. PMID:37735536^[4]

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

References

↑ Hoenderop JG, van der Kemp AW, Hartog A, van de Graaf SF, van Os CH, Willems PH, Bindels RJ. Molecular identification of the apical Ca2+ channel in 1, 25-dihydroxyvitamin D3-responsive epithelia. J Biol Chem. 1999 Mar 26;274(13):8375-8. PMID:10085067
↑ Nilius B, Vennekens R, Prenen J, Hoenderop JG, Droogmans G, Bindels RJ. The single pore residue Asp542 determines Ca2+ permeation and Mg2+ block of the epithelial Ca2+ channel. J Biol Chem. 2001 Jan 12;276(2):1020-5. PMID:11035011 doi:http://dx.doi.org/10.1074/jbc.M006184200
↑ Hoenderop JG, Voets T, Hoefs S, Weidema F, Prenen J, Nilius B, Bindels RJ. Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6. EMBO J. 2003 Feb 17;22(4):776-85. PMID:12574114 doi:http://dx.doi.org/10.1093/emboj/cdg080
↑ Lee BH, De Jesús Pérez JJ, Moiseenkova-Bell V, Rohacs T. Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A. Nat Commun. 2023 Sep 21;14(1):5883. PMID:37735536 doi:10.1038/s41467-023-41577-z

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8fhh"

Categories: Large Structures | Oryctolagus cuniculus | De Jesus-Perez JJ | Moiseenkova-Bell VY

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8fhh is ON HOLD
+==Wildtype rabbit TRPV5 in nanodiscs in the presence of oleoyl coenzyme A, Closed stated==
+<StructureSection load='8fhh' size='340' side='right'caption='[[8fhh]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8fhh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FHH FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.09&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ERG:ERGOSTEROL'>ERG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</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=8fhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fhh OCA], [https://pdbe.org/8fhh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fhh RCSB], [https://www.ebi.ac.uk/pdbsum/8fhh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fhh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/TRPV5_RABIT TRPV5_RABIT] Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12574114). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).[UniProtKB:P69744][UniProtKB:Q9NQA5]<ref>PMID:10085067</ref> <ref>PMID:11035011</ref> <ref>PMID:12574114</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Long-chain acyl-coenzyme A (LC-CoA) is a crucial metabolic intermediate that plays important cellular regulatory roles, including activation and inhibition of ion channels. The structural basis of ion channel regulation by LC-CoA is not known. Transient receptor potential vanilloid 5 and 6 (TRPV5 and TRPV6) are epithelial calcium-selective ion channels. Here, we demonstrate that LC-CoA activates TRPV5 and TRPV6 in inside-out patches, and both exogenously supplied and endogenously produced LC-CoA can substitute for the natural ligand phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) in maintaining channel activity in intact cells. Utilizing cryo-electron microscopy, we determined the structure of LC-CoA-bound TRPV5, revealing an open configuration with LC-CoA occupying the same binding site as PI(4,5)P(2) in previous studies. This is consistent with our finding that PI(4,5)P(2) could not further activate the channels in the presence of LC-CoA. Our data provide molecular insights into ion channel regulation by a metabolic signaling molecule.
-Authors:
+Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A.,Lee BH, De Jesus Perez JJ, Moiseenkova-Bell V, Rohacs T Nat Commun. 2023 Sep 21;14(1):5883. doi: 10.1038/s41467-023-41577-z. PMID:37735536<ref>PMID:37735536</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8fhh" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Oryctolagus cuniculus]]
+[[Category: De Jesus-Perez JJ]]
+[[Category: Moiseenkova-Bell VY]]

8fhh

From Proteopedia

Current revision

Wildtype rabbit TRPV5 in nanodiscs in the presence of oleoyl coenzyme A, Closed stated

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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