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==Cryo-EM structure of full-length TRPV1 at 4 degrees Celsius==
==Cryo-EM structure of full-length TRPV1 at 4 degrees Celsius==
<StructureSection load='7lp9' size='340' side='right'caption='[[7lp9]]' scene=''>
<StructureSection load='7lp9' size='340' side='right'caption='[[7lp9]], [[Resolution|resolution]] 2.63&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LP9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7lp9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LP9 FirstGlance]. <br>
</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=7lp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lp9 OCA], [https://pdbe.org/7lp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lp9 RCSB], [https://www.ebi.ac.uk/pdbsum/7lp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lp9 ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.63&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6OU:[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl]+(~{Z})-octadec-9-enoate'>6OU</scene>, <scene name='pdbligand=LBN:1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine'>LBN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=T7X:PHOSPHATIDYLINOSITOL'>T7X</scene>, <scene name='pdbligand=YFP:1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol'>YFP</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=7lp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lp9 OCA], [https://pdbe.org/7lp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lp9 RCSB], [https://www.ebi.ac.uk/pdbsum/7lp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lp9 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRPV1_RAT TRPV1_RAT] Receptor-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. May be involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis.<ref>PMID:9349813</ref> <ref>PMID:10644739</ref> <ref>PMID:11140687</ref> <ref>PMID:11418861</ref> <ref>PMID:12095983</ref> <ref>PMID:12194871</ref> <ref>PMID:12808128</ref> <ref>PMID:14523239</ref> <ref>PMID:12764195</ref> <ref>PMID:14630912</ref> <ref>PMID:15173182</ref> <ref>PMID:21076423</ref>
==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Kwon DH]]
[[Category: Kwon DH]]
[[Category: Lee S-Y]]
[[Category: Lee S-Y]]
[[Category: Suo Y]]
[[Category: Suo Y]]
[[Category: Zhang F]]
[[Category: Zhang F]]

Latest revision as of 17:59, 6 March 2024

Cryo-EM structure of full-length TRPV1 at 4 degrees CelsiusCryo-EM structure of full-length TRPV1 at 4 degrees Celsius

Structural highlights

7lp9 is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.63Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRPV1_RAT Receptor-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. May be involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]

See Also

References

  1. ↑ Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997 Oct 23;389(6653):816-24. PMID:9349813 doi:http://dx.doi.org/10.1038/39807
  2. ↑ Schumacher MA, Moff I, Sudanagunta SP, Levine JD. Molecular cloning of an N-terminal splice variant of the capsaicin receptor. Loss of N-terminal domain suggests functional divergence among capsaicin receptor subtypes. J Biol Chem. 2000 Jan 28;275(4):2756-62. PMID:10644739
  3. ↑ Premkumar LS, Ahern GP. Induction of vanilloid receptor channel activity by protein kinase C. Nature. 2000 Dec 21-28;408(6815):985-90. PMID:11140687 doi:http://dx.doi.org/10.1038/35050121
  4. ↑ Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature. 2001 Jun 21;411(6840):957-62. PMID:11418861 doi:http://dx.doi.org/10.1038/35082088
  5. ↑ Olah Z, Karai L, Iadarola MJ. Protein kinase C(alpha) is required for vanilloid receptor 1 activation. Evidence for multiple signaling pathways. J Biol Chem. 2002 Sep 20;277(38):35752-9. Epub 2002 Jul 2. PMID:12095983 doi:http://dx.doi.org/10.1074/jbc.M201551200
  6. ↑ Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW 4th. cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation. Neuron. 2002 Aug 15;35(4):721-31. PMID:12194871
  7. ↑ Numazaki M, Tominaga T, Takeuchi K, Murayama N, Toyooka H, Tominaga M. Structural determinant of TRPV1 desensitization interacts with calmodulin. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):8002-6. Epub 2003 Jun 13. PMID:12808128 doi:http://dx.doi.org/10.1073/pnas.1337252100
  8. ↑ Bhave G, Hu HJ, Glauner KS, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW 4th. Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12480-5. Epub 2003 Oct 1. PMID:14523239 doi:http://dx.doi.org/10.1073/pnas.2032100100
  9. ↑ Prescott ED, Julius D. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science. 2003 May 23;300(5623):1284-8. PMID:12764195 doi:http://dx.doi.org/10.1126/science.1083646
  10. ↑ Jung J, Shin JS, Lee SY, Hwang SW, Koo J, Cho H, Oh U. Phosphorylation of vanilloid receptor 1 by Ca2+/calmodulin-dependent kinase II regulates its vanilloid binding. J Biol Chem. 2004 Feb 20;279(8):7048-54. Epub 2003 Nov 20. PMID:14630912 doi:http://dx.doi.org/10.1074/jbc.M311448200
  11. ↑ Hellwig N, Plant TD, Janson W, Schafer M, Schultz G, Schaefer M. TRPV1 acts as proton channel to induce acidification in nociceptive neurons. J Biol Chem. 2004 Aug 13;279(33):34553-61. Epub 2004 Jun 1. PMID:15173182 doi:http://dx.doi.org/10.1074/jbc.M402966200
  12. ↑ Chavez AE, Chiu CQ, Castillo PE. TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat Neurosci. 2010 Dec;13(12):1511-8. doi: 10.1038/nn.2684. Epub 2010 Nov 14. PMID:21076423 doi:http://dx.doi.org/10.1038/nn.2684

7lp9, resolution 2.63Å

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