View source for 8jgv


==Cryo-EM structure of mClC-3_I607T with ATP==
<StructureSection load='8jgv' size='340' side='right'caption='[[8jgv]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jgv]] is a 2 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=8JGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JGV 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]] 2.98&#8491;</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=8jgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jgv OCA], [https://pdbe.org/8jgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jgv RCSB], [https://www.ebi.ac.uk/pdbsum/8jgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jgv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CLCN3_MOUSE CLCN3_MOUSE] May influence large dense-core vesicle exocytosis in adrenal chromaffin cells.<ref>PMID:16141072</ref>   Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (PubMed:26342074). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (By similarity). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity).[UniProtKB:P51790]<ref>PMID:26342074</ref>   Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (PubMed:24603049, PubMed:26342074, PubMed:28972156). Facilitates endosomal acidification and chloride accumulation in hepatocytes (PubMed:15504734).<ref>PMID:15504734</ref> <ref>PMID:24603049</ref> <ref>PMID:26342074</ref> <ref>PMID:28972156</ref>   Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons.<ref>PMID:26342074</ref> 
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== Publication Abstract from PubMed ==
The ClC-3 chloride/proton exchanger is both physiologically and pathologically critical, as it is potentiated by ATP to detect metabolic energy level and point mutations in ClC-3 lead to severe neurodegenerative diseases in human. However, why this exchanger is differentially modulated by ATP, ADP or AMP and how mutations caused gain-of-function remains largely unknow. Here we determine the high-resolution structures of dimeric wildtype ClC-3 in the apo state and in complex with ATP, ADP and AMP, and the disease-causing I607T mutant in the apo and ATP-bounded state by cryo-electron microscopy. In combination with patch-clamp recordings and molecular dynamic simulations, we reveal how the adenine nucleotides binds to ClC-3 and changes in ion occupancy between apo and ATP-bounded state. We further observe I607T mutation induced conformational changes and augments in current. Therefore, our study not only lays the structural basis of adenine nucleotides regulation in ClC-3, but also clearly indicates the target region for drug discovery against ClC-3 mediated neurodegenerative diseases.

Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.,Wan Y, Guo S, Zhen W, Xu L, Chen X, Liu F, Shen Y, Liu S, Hu L, Wang X, Ye F, Wang Q, Wen H, Yang F Nat Commun. 2024 Aug 6;15(1):6654. doi: 10.1038/s41467-024-50975-w. PMID:39107281<ref>PMID:39107281</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Wan YZQ]]
[[Category: Yang F]]