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| | ==Structure of the nvTRPM2 channel in complex with Ca2+== | | ==Structure of the nvTRPM2 channel in complex with Ca2+== |
| - | <StructureSection load='6co7' size='340' side='right' caption='[[6co7]], [[Resolution|resolution]] 3.07Å' scene=''> | + | <SX load='6co7' size='340' side='right' viewer='molstar' caption='[[6co7]], [[Resolution|resolution]] 3.07Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6co7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Nemve Nemve]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CO7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CO7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6co7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Nematostella_vectensis Nematostella vectensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CO7 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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</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]] 3.07Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">v1g248535 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=45351 NEMVE])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></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=6co7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6co7 OCA], [http://pdbe.org/6co7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6co7 RCSB], [http://www.ebi.ac.uk/pdbsum/6co7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6co7 ProSAT]</span></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=6co7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6co7 OCA], [https://pdbe.org/6co7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6co7 RCSB], [https://www.ebi.ac.uk/pdbsum/6co7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6co7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TMP2L_NEMVE TMP2L_NEMVE] Nonselective, voltage-independent cation channel that mediates Ca(2+) and to a lesser extent Na(+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897). Functions as a ligand-gated ion channel (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897). Binding of ADP-ribose causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897). May have ADP-ribose pyrophosphatase activity which reduces ADP-ribose levels induced by oxidative stress, thus preventing the channel activation by reactive oxygen species (PubMed:25620041, PubMed:27333281).<ref>PMID:25620041</ref> <ref>PMID:27333281</ref> <ref>PMID:28775320</ref> <ref>PMID:29745897</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| - | [[Category: Nemve]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, J]]
| + | |
| - | [[Category: Csanady, L]]
| + | |
| - | [[Category: Szollosi, A]]
| + | |
| - | [[Category: Toth, B]]
| + | |
| - | [[Category: Zhang, Z]]
| + | |
| - | [[Category: Ca2+ binding]]
| + | |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| | [[Category: Nematostella vectensis]] | | [[Category: Nematostella vectensis]] |
| - | [[Category: Trpm2]] | + | [[Category: Chen J]] |
| | + | [[Category: Csanady L]] |
| | + | [[Category: Szollosi A]] |
| | + | [[Category: Toth B]] |
| | + | [[Category: Zhang Z]] |
| Structural highlights
Function
TMP2L_NEMVE Nonselective, voltage-independent cation channel that mediates Ca(2+) and to a lesser extent Na(+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897). Functions as a ligand-gated ion channel (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897). Binding of ADP-ribose causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897). May have ADP-ribose pyrophosphatase activity which reduces ADP-ribose levels induced by oxidative stress, thus preventing the channel activation by reactive oxygen species (PubMed:25620041, PubMed:27333281).[1] [2] [3] [4]
Publication Abstract from PubMed
Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel required for immune cell activation, insulin secretion, and body heat control. TRPM2 is activated by cytosolic Ca(2+), phosphatidyl-inositol-4,5-bisphosphate and ADP ribose. Here we present the ~3A resolution electron cryo-microscopy structure of TRPM2 from Nematostella vectensis, 63% similar in sequence to human TRPM2, in the Ca(2+)-bound closed state. Compared to other TRPM channels, TRPM2 exhibits unique structural features that correlate with its function. The pore is larger and more negatively charged, consistent with its high Ca(2+) selectivity and larger conductance. The intracellular Ca(2+) binding sites are connected to the pore and cytosol, explaining the unusual dependence of TRPM2 activity on intra- and extracellular Ca(2+). In addition, the absence of a post-filter motif is likely the cause of the rapid inactivation of human TRPM2. Together, our cryo-EM and electrophysiology studies provide a molecular understanding of the unique gating mechanism of TRPM2.
Structure of a TRPM2 channel in complex with Ca(2+) explains unique gating regulation.,Zhang Z, Toth B, Szollosi A, Chen J, Csanady L Elife. 2018 May 10;7. pii: 36409. doi: 10.7554/eLife.36409. PMID:29745897[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kühn FJ, Kühn C, Lückhoff A. Functional characterisation of a TRPM2 orthologue from the sea anemone Nematostella vectensis in human cells. Sci Rep. 2015 Jan 26;5:8032. PMID:25620041 doi:10.1038/srep08032
- ↑ Kühn FJ, Kühn C, Winking M, Hoffmann DC, Lückhoff A. ADP-Ribose Activates the TRPM2 Channel from the Sea Anemone Nematostella vectensis Independently of the NUDT9H Domain. PLoS One. 2016 Jun 22;11(6):e0158060. PMID:27333281 doi:10.1371/journal.pone.0158060
- ↑ Kühn FJP, Mathis W, Cornelia K, Hoffmann DC, Lückhoff A. Modulation of activation and inactivation by Ca(2+) and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis. Sci Rep. 2017 Aug 3;7(1):7245. PMID:28775320 doi:10.1038/s41598-017-07652-4
- ↑ Zhang Z, Toth B, Szollosi A, Chen J, Csanady L. Structure of a TRPM2 channel in complex with Ca(2+) explains unique gating regulation. Elife. 2018 May 10;7. pii: 36409. doi: 10.7554/eLife.36409. PMID:29745897 doi:http://dx.doi.org/10.7554/eLife.36409
- ↑ Zhang Z, Toth B, Szollosi A, Chen J, Csanady L. Structure of a TRPM2 channel in complex with Ca(2+) explains unique gating regulation. Elife. 2018 May 10;7. pii: 36409. doi: 10.7554/eLife.36409. PMID:29745897 doi:http://dx.doi.org/10.7554/eLife.36409
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