5wp6

From Proteopedia

(Difference between revisions)

Revision as of 06:57, 29 March 2023

Cryo-EM structure of a human TRPM4 channel in complex with calcium and decavanadate

5wp6, resolution 3.80Å

Structural highlights

5wp6 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TRPM4_HUMAN Familial progressive cardiac conduction defect;Brugada syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

TRPM4_HUMAN Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

Ca(2+)-activated, non-selective (CAN) ion channels sense increases of the intracellular Ca(2+) concentration, producing a flux of Na(+) and/or K(+) ions that depolarizes the cell, thus modulating cellular Ca(2+) entry. CAN channels are involved in cellular responses such as neuronal bursting activity and cardiac rhythm. Here we report the electron cryo-microscopy structure of the most widespread CAN channel, human TRPM4, bound to the agonist Ca(2+) and the modulator decavanadate. Four cytosolic C-terminal domains form an umbrella-like structure with a coiled-coil domain for the 'pole' and four helical 'ribs' spanning the N-terminal TRPM homology regions (MHRs), thus holding four subunits in a crown-like architecture. We observed two decavanadate-binding sites, one in the C-terminal domain and another in the intersubunit MHR interface. A glutamine in the selectivity filter may be an important determinant of monovalent selectivity. Our structure provides new insights into the function and pharmacology of both the CAN and the TRPM families.

Electron cryo-microscopy structure of a human TRPM4 channel.,Winkler PA, Huang Y, Sun W, Du J, Lu W Nature. 2017 Dec 14;552(7684):200-204. doi: 10.1038/nature24674. Epub 2017 Dec 6. PMID:29211723^[9]

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

References

↑ Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP. TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell. 2002 May 3;109(3):397-407. PMID:12015988
↑ Nilius B, Prenen J, Droogmans G, Voets T, Vennekens R, Freichel M, Wissenbach U, Flockerzi V. Voltage dependence of the Ca2+-activated cation channel TRPM4. J Biol Chem. 2003 Aug 15;278(33):30813-20. Epub 2003 Jun 10. PMID:12799367 doi:http://dx.doi.org/10.1074/jbc.M305127200
↑ Guinamard R, Chatelier A, Demion M, Potreau D, Patri S, Rahmati M, Bois P. Functional characterization of a Ca(2+)-activated non-selective cation channel in human atrial cardiomyocytes. J Physiol. 2004 Jul 1;558(Pt 1):75-83. Epub 2004 Apr 30. PMID:15121803 doi:http://dx.doi.org/10.1113/jphysiol.2004.063974
↑ Earley S, Waldron BJ, Brayden JE. Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries. Circ Res. 2004 Oct 29;95(9):922-9. Epub 2004 Oct 7. PMID:15472118 doi:http://dx.doi.org/01.RES.0000147311.54833.03
↑ Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet JP. TRPM4 regulates calcium oscillations after T cell activation. Science. 2004 Nov 19;306(5700):1374-7. doi: 10.1126/science.1098845. PMID:15550671 doi:http://dx.doi.org/10.1126/science.1098845
↑ Cheng H, Beck A, Launay P, Gross SA, Stokes AJ, Kinet JP, Fleig A, Penner R. TRPM4 controls insulin secretion in pancreatic beta-cells. Cell Calcium. 2007 Jan;41(1):51-61. Epub 2006 Jun 27. PMID:16806463 doi:http://dx.doi.org/S0143-4160(06)00105-9
↑ Armisen R, Marcelain K, Simon F, Tapia JC, Toro J, Quest AF, Stutzin A. TRPM4 enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. J Cell Physiol. 2011 Jan;226(1):103-9. doi: 10.1002/jcp.22310. PMID:20625999 doi:http://dx.doi.org/10.1002/jcp.22310
↑ Weber KS, Hildner K, Murphy KM, Allen PM. Trpm4 differentially regulates Th1 and Th2 function by altering calcium signaling and NFAT localization. J Immunol. 2010 Sep 1;185(5):2836-46. doi: 10.4049/jimmunol.1000880. Epub 2010, Jul 23. PMID:20656926 doi:http://dx.doi.org/10.4049/jimmunol.1000880
↑ Winkler PA, Huang Y, Sun W, Du J, Lu W. Electron cryo-microscopy structure of a human TRPM4 channel. Nature. 2017 Dec 14;552(7684):200-204. doi: 10.1038/nature24674. Epub 2017 Dec 6. PMID:29211723 doi:http://dx.doi.org/10.1038/nature24674

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5wp6"

@@ Line 3: / Line 3: @@
 <SX load='5wp6' size='340' side='right' viewer='molstar' caption='[[5wp6]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5wp6]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WP6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WP6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5wp6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WP6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WP6 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DVT:DECAVANADATE'>DVT</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRPM4, LTRPC4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5wp6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wp6 OCA], [https://pdbe.org/5wp6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wp6 RCSB], [https://www.ebi.ac.uk/pdbsum/5wp6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wp6 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5wp6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wp6 OCA], [http://pdbe.org/5wp6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wp6 RCSB], [http://www.ebi.ac.uk/pdbsum/5wp6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wp6 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/TRPM4_HUMAN TRPM4_HUMAN]] Familial progressive cardiac conduction defect;Brugada syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/TRPM4_HUMAN TRPM4_HUMAN] Familial progressive cardiac conduction defect;Brugada syndrome. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/TRPM4_HUMAN TRPM4_HUMAN]] Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway.<ref>PMID:12015988</ref> <ref>PMID:12799367</ref> <ref>PMID:15121803</ref> <ref>PMID:15472118</ref> <ref>PMID:15550671</ref> <ref>PMID:16806463</ref> <ref>PMID:20625999</ref> <ref>PMID:20656926</ref>
+[https://www.uniprot.org/uniprot/TRPM4_HUMAN TRPM4_HUMAN] Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway.<ref>PMID:12015988</ref> <ref>PMID:12799367</ref> <ref>PMID:15121803</ref> <ref>PMID:15472118</ref> <ref>PMID:15550671</ref> <ref>PMID:16806463</ref> <ref>PMID:20625999</ref> <ref>PMID:20656926</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 24: @@
 __TOC__
 </SX>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Du, J]]
+[[Category: Du J]]
-[[Category: Huang, Y]]
+[[Category: Huang Y]]
-[[Category: Lu, W]]
+[[Category: Lu W]]
-[[Category: Sun, W]]
+[[Category: Sun W]]
-[[Category: Winkler, P A]]
+[[Category: Winkler PA]]
-[[Category: Ion channel]]
-[[Category: Membrane protein]]

5wp6

From Proteopedia

Revision as of 06:57, 29 March 2023

Cryo-EM structure of a human TRPM4 channel in complex with calcium and decavanadate

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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