View source for 8inz


==Cryo-EM structure of human HCN3 channel in apo state==
<StructureSection load='8inz' size='340' side='right'caption='[[8inz]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8inz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8INZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8INZ 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]] 2.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VX9:4-[[(2~{S},4~{a}~{R},6~{S},8~{a}~{S})-6-[(4~{S},5~{R})-4-[(2~{S})-butan-2-yl]-5,9-dimethyl-decyl]-4~{a}-methyl-2,3,4,5,6,7,8,8~{a}-octahydro-1~{H}-naphthalen-2-yl]oxy]-4-oxidanylidene-butanoic+acid'>VX9</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=8inz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8inz OCA], [https://pdbe.org/8inz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8inz RCSB], [https://www.ebi.ac.uk/pdbsum/8inz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8inz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HCN3_HUMAN HCN3_HUMAN] Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions.<ref>PMID:16043489</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level. The results of our study could help to design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.

Cryo-EM structure of human HCN3 channel and its regulation by cAMP.,Yu B, Lu Q, Li J, Cheng X, Hu H, Li Y, Che T, Hua Y, Jiang H, Zhang Y, Xian C, Yang T, Fu Y, Chen Y, Nan W, McCormick PJ, Xiong B, Duan J, Zeng B, Li Y, Fu Y, Zhang J J Biol Chem. 2024 Jun;300(6):107288. doi: 10.1016/j.jbc.2024.107288. Epub 2024 , Apr 16. PMID:38636662<ref>PMID:38636662</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8inz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li J]]
[[Category: Lu QY]]
[[Category: Yu B]]
[[Category: Zhang J]]