6l93: Difference between revisions

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'''Unreleased structure'''


The entry 6l93 is ON HOLD until Paper Publication
==X-ray structure of the ligand-free human TRPV1 ankyrin repeat domain==
<StructureSection load='6l93' size='340' side='right'caption='[[6l93]], [[Resolution|resolution]] 4.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6l93]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6L93 FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6l93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l93 OCA], [http://pdbe.org/6l93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l93 RCSB], [http://www.ebi.ac.uk/pdbsum/6l93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l93 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/TRPV1_HUMAN TRPV1_HUMAN]] Ligand-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. 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.[UniProtKB:O35433]<ref>PMID:11050376</ref> <ref>PMID:11226139</ref> <ref>PMID:11243859</ref> <ref>PMID:12077606</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
TRPV1, a member of the transient receptor potential (TRP) channels family, has been found to be involved in redox sensing. The crystal structure of the human TRPV1 ankyrin-repeat domain (TRPV1-ARD) was determined at 4.5 A resolution under nonreducing conditions. This is the first report of the crystal structure of a ligand-free form of TRPV1-ARD and in particular of the human homologue. The structure showed a unique conformation in finger loop 3 near Cys258, which is most likely to be involved in inter-subunit disulfide-bond formation. Also, in human TRPV1-ARD it was possible for solvent to access Cys258. This structural feature might be related to the high sensitivity of human TRPV1 to oxidants. ESI-MS revealed that Cys258 did not form an S-OH functionality even under nonreducing conditions.


Authors: Tanaka, M., Hayakawa, K., Unno, M.
Structure determination of the human TRPV1 ankyrin-repeat domain under nonreducing conditions.,Tanaka M, Hayakawa K, Ogawa N, Kurokawa T, Kitanishi K, Ite K, Matsui T, Mori Y, Unno M Acta Crystallogr F Struct Biol Commun. 2020 Mar 1;76(Pt 3):130-137. doi:, 10.1107/S2053230X20001533. Epub 2020 Mar 2. PMID:32133998<ref>PMID:32133998</ref>


Description: X-ray structure of the ligand-free human TRPV1 ankyrin repeat domain
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6l93" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Hayakawa, K]]
[[Category: Tanaka, M]]
[[Category: Tanaka, M]]
[[Category: Hayakawa, K]]
[[Category: Unno, M]]
[[Category: Unno, M]]
[[Category: Channel domain]]
[[Category: Transport protein]]

Revision as of 12:40, 18 March 2020

X-ray structure of the ligand-free human TRPV1 ankyrin repeat domainX-ray structure of the ligand-free human TRPV1 ankyrin repeat domain

Structural highlights

6l93 is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TRPV1_HUMAN] Ligand-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. 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.[UniProtKB:O35433][1] [2] [3] [4]

Publication Abstract from PubMed

TRPV1, a member of the transient receptor potential (TRP) channels family, has been found to be involved in redox sensing. The crystal structure of the human TRPV1 ankyrin-repeat domain (TRPV1-ARD) was determined at 4.5 A resolution under nonreducing conditions. This is the first report of the crystal structure of a ligand-free form of TRPV1-ARD and in particular of the human homologue. The structure showed a unique conformation in finger loop 3 near Cys258, which is most likely to be involved in inter-subunit disulfide-bond formation. Also, in human TRPV1-ARD it was possible for solvent to access Cys258. This structural feature might be related to the high sensitivity of human TRPV1 to oxidants. ESI-MS revealed that Cys258 did not form an S-OH functionality even under nonreducing conditions.

Structure determination of the human TRPV1 ankyrin-repeat domain under nonreducing conditions.,Tanaka M, Hayakawa K, Ogawa N, Kurokawa T, Kitanishi K, Ite K, Matsui T, Mori Y, Unno M Acta Crystallogr F Struct Biol Commun. 2020 Mar 1;76(Pt 3):130-137. doi:, 10.1107/S2053230X20001533. Epub 2020 Mar 2. PMID:32133998[5]

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

References

  1. ↑ Hayes P, Meadows HJ, Gunthorpe MJ, Harries MH, Duckworth DM, Cairns W, Harrison DC, Clarke CE, Ellington K, Prinjha RK, Barton AJ, Medhurst AD, Smith GD, Topp S, Murdock P, Sanger GJ, Terrett J, Jenkins O, Benham CD, Randall AD, Gloger IS, Davis JB. Cloning and functional expression of a human orthologue of rat vanilloid receptor-1. Pain. 2000 Nov;88(2):205-15. doi: 10.1016/s0304-3959(00)00353-5. PMID:11050376 doi:http://dx.doi.org/10.1016/s0304-3959(00)00353-5
  2. ↑ McIntyre P, McLatchie LM, Chambers A, Phillips E, Clarke M, Savidge J, Toms C, Peacock M, Shah K, Winter J, Weerasakera N, Webb M, Rang HP, Bevan S, James IF. Pharmacological differences between the human and rat vanilloid receptor 1 (VR1). Br J Pharmacol. 2001 Mar;132(5):1084-94. doi: 10.1038/sj.bjp.0703918. PMID:11226139 doi:http://dx.doi.org/10.1038/sj.bjp.0703918
  3. ↑ Cortright DN, Crandall M, Sanchez JF, Zou T, Krause JE, White G. The tissue distribution and functional characterization of human VR1. Biochem Biophys Res Commun. 2001 Mar;281(5):1183-9. PMID:11243859 doi:http://dx.doi.org/10.1006/bbrc.2001.4482
  4. ↑ Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, Facer P, Wright JE, Jerman JC, Walhin JP, Ooi L, Egerton J, Charles KJ, Smart D, Randall AD, Anand P, Davis JB. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature. 2002 Jul 11;418(6894):186-90. doi: 10.1038/nature00894. Epub 2002 Jun 23. PMID:12077606 doi:http://dx.doi.org/10.1038/nature00894
  5. ↑ Tanaka M, Hayakawa K, Ogawa N, Kurokawa T, Kitanishi K, Ite K, Matsui T, Mori Y, Unno M. Structure determination of the human TRPV1 ankyrin-repeat domain under nonreducing conditions. Acta Crystallogr F Struct Biol Commun. 2020 Mar 1;76(Pt 3):130-137. doi:, 10.1107/S2053230X20001533. Epub 2020 Mar 2. PMID:32133998 doi:http://dx.doi.org/10.1107/S2053230X20001533

6l93, resolution 4.47Å

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