6bwi

From Proteopedia

(Difference between revisions)

Revision as of 12:29, 6 November 2024

3.7 angstrom cryoEM structure of full length human TRPM4

6bwi, resolution 3.70Å

Structural highlights

6bwi 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.
Method:	Electron Microscopy, Resolution 3.7Å
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

Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na(+)-bound, apo state at pH 7.5 to an overall resolution of 3.7 A. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini. Finally, we identify aromatic interactions via pi-pi bonds and cation-pi bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites. We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.

Structure of full-length human TRPM4.,Duan J, Li Z, Li J, Santa-Cruz A, Sanchez-Martinez S, Zhang J, Clapham DE Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2377-2382. doi:, 10.1073/pnas.1722038115. Epub 2018 Feb 20. PMID:29463718^[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
↑ Duan J, Li Z, Li J, Santa-Cruz A, Sanchez-Martinez S, Zhang J, Clapham DE. Structure of full-length human TRPM4. Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2377-2382. doi:, 10.1073/pnas.1722038115. Epub 2018 Feb 20. PMID:29463718 doi:http://dx.doi.org/10.1073/pnas.1722038115

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/6bwi"

@@ Line 3: / Line 3: @@
 <SX load='6bwi' size='340' side='right' viewer='molstar' caption='[[6bwi]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6bwi]] 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=6BWI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BWI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6bwi]] 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=6BWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BWI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></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]] 3.7&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=6bwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bwi OCA], [https://pdbe.org/6bwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bwi RCSB], [https://www.ebi.ac.uk/pdbsum/6bwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bwi 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=6bwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bwi OCA], [http://pdbe.org/6bwi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bwi RCSB], [http://www.ebi.ac.uk/pdbsum/6bwi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bwi ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[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 ==
+[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 22: / Line 25: @@
 __TOC__
 </SX>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Clapham, D E]]
+[[Category: Clapham DE]]
-[[Category: Duan, J]]
+[[Category: Duan J]]
-[[Category: Li, J]]
+[[Category: Li J]]
-[[Category: Li, Z]]
+[[Category: Li Z]]
-[[Category: Zhang, J]]
+[[Category: Zhang J]]
-[[Category: Cryoem]]
-[[Category: Human full length trpm7]]
-[[Category: Membrane protein]]

6bwi

From Proteopedia

Revision as of 12:29, 6 November 2024

3.7 angstrom cryoEM structure of full length human TRPM4

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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