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| | <SX load='6drj' size='340' side='right' viewer='molstar' caption='[[6drj]], [[Resolution|resolution]] 3.30Å' scene=''> | | <SX load='6drj' size='340' side='right' viewer='molstar' caption='[[6drj]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6drj]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DRJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DRJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6drj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DRJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DRJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 3.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">trpm2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=6drj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6drj OCA], [http://pdbe.org/6drj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6drj RCSB], [http://www.ebi.ac.uk/pdbsum/6drj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6drj 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=6drj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6drj OCA], [https://pdbe.org/6drj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6drj RCSB], [https://www.ebi.ac.uk/pdbsum/6drj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6drj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TRPM2_DANRE TRPM2_DANRE] Nonselective, voltage-independent cation channel that mediates Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels. Functions as a ligand-gated ion channel. Binding of ADP-ribose to the cytoplasmic N-terminal region causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening.<ref>PMID:30250252</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| | [[Category: Large Structures]] | | [[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]] | + | [[Category: Winkler P]] |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
TRPM2_DANRE Nonselective, voltage-independent cation channel that mediates Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels. Functions as a ligand-gated ion channel. Binding of ADP-ribose to the cytoplasmic N-terminal region causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening.[1]
Publication Abstract from PubMed
Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that has an essential role in diverse physiological processes such as core body temperature regulation, immune response and apoptosis(1-4). TRPM2 is polymodal and can be activated by a wide range of stimuli(1-7), including temperature, oxidative stress and NAD(+)-related metabolites such as ADP-ribose (ADPR). Its activation results in both Ca(2+) entry across the plasma membrane and Ca(2+) release from lysosomes(8), and has been linked to diseases such as ischaemia-reperfusion injury, bipolar disorder and Alzheimer's disease(9-11). Here we report the cryo-electron microscopy structures of the zebrafish TRPM2 in the apo resting (closed) state and in the ADPR/Ca(2+)-bound active (open) state, in which the characteristic NUDT9-H domains hang underneath the MHR1/2 domain. We identify an ADPR-binding site located in the bi-lobed structure of the MHR1/2 domain. Our results provide an insight into the mechanism of activation of the TRPM channel family and define a framework for the development of therapeutic agents to treat neurodegenerative diseases and temperature-related pathological conditions.
Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium.,Huang Y, Winkler PA, Sun W, Lu W, Du J Nature. 2018 Oct;562(7725):145-149. doi: 10.1038/s41586-018-0558-4. Epub 2018 Sep, 24. PMID:30250252[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang Y, Winkler PA, Sun W, Lu W, Du J. Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. Nature. 2018 Oct;562(7725):145-149. doi: 10.1038/s41586-018-0558-4. Epub 2018 Sep, 24. PMID:30250252 doi:http://dx.doi.org/10.1038/s41586-018-0558-4
- ↑ Huang Y, Winkler PA, Sun W, Lu W, Du J. Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. Nature. 2018 Oct;562(7725):145-149. doi: 10.1038/s41586-018-0558-4. Epub 2018 Sep, 24. PMID:30250252 doi:http://dx.doi.org/10.1038/s41586-018-0558-4
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