View source for 8si4


==Cryo-EM structure of TRPM7 N1098Q mutant in GDN detergent in open state==
<StructureSection load='8si4' size='340' side='right'caption='[[8si4]], [[Resolution|resolution]] 2.46&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8si4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SI4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SI4 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]] 2.46&#8491;</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=DU0:2-[2-[(1~{S},2~{S},4~{S},5~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5,7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2-oxane]-16-yl]oxyethyl]propane-1,3-diol'>DU0</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'>[https://proteopedia.org/fgij/fg.htm?mol=8si4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8si4 OCA], [https://pdbe.org/8si4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8si4 RCSB], [https://www.ebi.ac.uk/pdbsum/8si4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8si4 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The transient receptor potential channel TRPM7 is a master regulator of the organismal balance of divalent cations that plays an essential role in embryonic development, immune responses, cell mobility, proliferation, and differentiation. TRPM7 is implicated in neuronal and cardiovascular disorders, tumor progression and has emerged as a new drug target. Here we use cryo-EM, functional analysis, and molecular dynamics simulations to uncover two distinct structural mechanisms of TRPM7 activation by a gain-of-function mutation and by the agonist naltriben, which show different conformational dynamics and domain involvement. We identify a binding site for highly potent and selective inhibitors and show that they act by stabilizing the TRPM7 closed state. The discovered structural mechanisms provide foundations for understanding the molecular basis of TRPM7 channelopathies and drug development.

Structural mechanisms of TRPM7 activation and inhibition.,Nadezhdin KD, Correia L, Narangoda C, Patel DS, Neuberger A, Gudermann T, Kurnikova MG, Chubanov V, Sobolevsky AI Nat Commun. 2023 May 8;14(1):2639. doi: 10.1038/s41467-023-38362-3. PMID:37156763<ref>PMID:37156763</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8si4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Nadezhdin KD]]
[[Category: Neuberger A]]
[[Category: Sobolevsky AI]]