8ffo

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of wildtype rabbit TRPV5 with PI(4,5)P2 in nanodiscs

Structural highlights

8ffo 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 3.5Å
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/8ffo"

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

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8ffo is ON HOLD  until Paper Publication
+==Cryo-EM structure of wildtype rabbit TRPV5 with PI(4,5)P2 in nanodiscs==
+<StructureSection load='8ffo' size='340' side='right'caption='[[8ffo]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8ffo]] 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=8FFO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FFO 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]] 3.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPL:1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>CPL</scene>, <scene name='pdbligand=ERG:ERGOSTEROL'>ERG</scene>, <scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</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=8ffo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ffo OCA], [https://pdbe.org/8ffo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ffo RCSB], [https://www.ebi.ac.uk/pdbsum/8ffo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ffo 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 8ffo" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Oryctolagus cuniculus]]
+[[Category: De Jesus-Perez JJ]]
+[[Category: Moiseenkova-Bell VY]]

8ffo

From Proteopedia

Current revision

Cryo-EM structure of wildtype rabbit TRPV5 with PI(4,5)P2 in nanodiscs

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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