View source for 6o77


==Structure of the TRPM8 cold receptor by single particle electron cryo-microscopy, calcium-bound state==
<SX load='6o77' size='340' side='right' viewer='molstar' caption='[[6o77]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6o77]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Parus_major Parus major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O77 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O77 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]] 3.2&#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=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=6o77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o77 OCA], [https://pdbe.org/6o77 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o77 RCSB], [https://www.ebi.ac.uk/pdbsum/6o77 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o77 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary detector of environmental cold and an important target for treating pathological cold hypersensitivity. Here, we present cryo-electron microscopy structures of TRPM8 in ligand-free, antagonist-bound, or calcium-bound forms, revealing how robust conformational changes give rise to two nonconducting states, closed and desensitized. We describe a malleable ligand-binding pocket that accommodates drugs of diverse chemical structures, and we delineate the ion permeation pathway, including the contribution of lipids to pore architecture. Furthermore, we show that direct calcium binding mediates stimulus-evoked desensitization, clarifying this important mechanism of sensory adaptation. We observe large rearrangements within the S4-S5 linker that reposition the S1-S4 and pore domains relative to the TRP helix, leading us to propose a distinct model for modulation of TRPM8 and possibly other TRP channels.

Structural insights into TRPM8 inhibition and desensitization.,Diver MM, Cheng Y, Julius D Science. 2019 Sep 27;365(6460):1434-1440. doi: 10.1126/science.aax6672. Epub 2019, Sep 5. PMID:31488702<ref>PMID:31488702</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 6o77" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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[[Category: Large Structures]]
[[Category: Parus major]]
[[Category: Cheng Y]]
[[Category: Diver MM]]
[[Category: Julius D]]