View source for 6pkx


==Cryo-EM structure of the zebrafish TRPM2 channel in the presence of ADPR and Ca2+==
<SX load='6pkx' size='340' side='right' viewer='molstar' caption='[[6pkx]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pkx]] 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=6PKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PKX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</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'>[https://proteopedia.org/fgij/fg.htm?mol=6pkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pkx OCA], [https://pdbe.org/6pkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pkx RCSB], [https://www.ebi.ac.uk/pdbsum/6pkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pkx ProSAT]</span></td></tr>
</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> 
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== Publication Abstract from PubMed ==
The transient receptor potential melastatin 2 (TRPM2) channel plays a key role in redox sensation in many cell types. Channel activation requires binding of both ADP-ribose (ADPR) and Ca(2+). The recently published TRPM2 structures from Danio rerio in the ligand-free and the ADPR/Ca(2+)-bound conditions represent the channel in closed and open states, which uncovered substantial tertiary and quaternary conformational rearrangements. However, it is unclear how these rearrangements are achieved within the tetrameric channel during channel gating. Here we report the cryo-electron microscopy structures of Danio rerio TRPM2 in the absence of ligands, in complex with Ca(2+) alone, and with both ADPR and Ca(2+), resolved to ~4.3 A, ~3.8 A, and ~4.2 A, respectively. In contrast to the published results, our studies capture ligand-bound TRPM2 structures in two-fold symmetric intermediate states, offering a glimpse of the structural transitions that bridge the closed and open conformations.

Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel.,Yin Y, Wu M, Hsu AL, Borschel WF, Borgnia MJ, Lander GC, Lee SY Nat Commun. 2019 Aug 20;10(1):3740. doi: 10.1038/s41467-019-11733-5. PMID:31431622<ref>PMID:31431622</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6pkx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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[[Category: Danio rerio]]
[[Category: Large Structures]]
[[Category: Borgnia MJ]]
[[Category: Borschel WF]]
[[Category: Hsu AL]]
[[Category: Lander GC]]
[[Category: Lee S-Y]]
[[Category: Wu M]]
[[Category: Yin Y]]