3sui

From Proteopedia

(Difference between revisions)

Revision as of 15:49, 4 August 2016

Crystal structure of ca2+-calmodulin in complex with a trpv1 c-terminal peptide

Structural highlights

3sui is a 2 chain structure with sequence from Buffalo rat and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	CALM, CALM1, CALM2, CALM3, CALML2, CAM, CAM1, CAM2, CAM3, CAMB, CAMC, CAMIII (HUMAN), Trpv1, Vr1, Vr1l (Buffalo rat)
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]

Publication Abstract from PubMed

Transient receptor potential (TRP) vanilloid 1 (TRPV1) is a molecular pain receptor belonging to the TRP superfamily of nonselective cation channels. As a polymodal receptor, TRPV1 responds to heat and a wide range of chemical stimuli. The influx of calcium after channel activation serves as a negative feedback mechanism leading to TRPV1 desensitization. The cellular calcium sensor calmodulin (CaM) likely participates in the desensitization of TRPV1. Two CaM-binding sites are identified in TRPV1: the N-terminal ankyrin repeat domain (ARD) and a short distal C-terminal (CT) segment. Here, we present the crystal structure of calcium-bound CaM (Ca(2+)-CaM) in complex with the TRPV1-CT segment, determined to 1.95-A resolution. The two lobes of Ca(2+)-CaM wrap around a helical TRPV1-CT segment in an antiparallel orientation, and two hydrophobic anchors, W787 and L796, contact the C-lobe and N-lobe of Ca(2+)-CaM, respectively. This structure is similar to canonical Ca(2+)-CaM-peptide complexes, although TRPV1 contains no classical CaM recognition sequence motif. Using structural and mutational studies, we established the TRPV1 C terminus as a high affinity Ca(2+)-CaM-binding site in both the isolated TRPV1 C terminus and in full-length TRPV1. Although a ternary complex of CaM, TRPV1-ARD, and TRPV1-CT had previously been postulated, we found no biochemical evidence of such a complex. In electrophysiology studies, mutation of the Ca(2+)-CaM-binding site on TRPV1-ARD abolished desensitization in response to repeated application of capsaicin, whereas mutation of the Ca(2+)-CaM-binding site in TRPV1-CT led to a more subtle phenotype of slowed and reduced TRPV1 desensitization. In summary, our results show that the TRPV1-ARD is an important mediator of TRPV1 desensitization, whereas TRPV1-CT has higher affinity for CaM and is likely involved in separate regulatory mechanisms.

Distinct properties of Ca2+-calmodulin binding to N- and C-terminal regulatory regions of the TRPV1 channel.,Lau SY, Procko E, Gaudet R J Gen Physiol. 2012 Nov;140(5):541-55. doi: 10.1085/jgp.201210810. PMID:23109716^[13]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Lau SY, Procko E, Gaudet R. Distinct properties of Ca2+-calmodulin binding to N- and C-terminal regulatory regions of the TRPV1 channel. J Gen Physiol. 2012 Nov;140(5):541-55. doi: 10.1085/jgp.201210810. PMID:23109716 doi:http://dx.doi.org/10.1085/jgp.201210810

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3sui"

@@ Line 1: / Line 1: @@
 ==Crystal structure of ca2+-calmodulin in complex with a trpv1 c-terminal peptide==
 <StructureSection load='3sui' size='340' side='right' caption='[[3sui]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3sui]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SUI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SUI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3sui]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SUI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SUI FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALM, CALM1, CALM2, CALM3, CALML2, CAM, CAM1, CAM2, CAM3, CAMB, CAMC, CAMIII ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), Trpv1, Vr1, Vr1l ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALM, CALM1, CALM2, CALM3, CALML2, CAM, CAM1, CAM2, CAM3, CAMB, CAMC, CAMIII ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Trpv1, Vr1, Vr1l ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3sui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sui OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sui RCSB], [http://www.ebi.ac.uk/pdbsum/3sui PDBsum]</span></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=3sui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sui OCA], [http://pdbe.org/3sui PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sui RCSB], [http://www.ebi.ac.uk/pdbsum/3sui PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sui ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3sui" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Buffalo rat]]
-[[Category: Rattus norvegicus]]
+[[Category: Human]]
 [[Category: Gaudet, R]]
 [[Category: Lau, S Y]]

3sui

From Proteopedia

Revision as of 15:49, 4 August 2016

Crystal structure of ca2+-calmodulin in complex with a trpv1 c-terminal peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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