9dnx

From Proteopedia

(Difference between revisions)

Current revision

Human ClC-3:TMEM9, TMEM9 Protomer A and B: Complete

Structural highlights

9dnx is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.86Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CLCN3_HUMAN Non-specific syndromic intellectual disability. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

CLCN3_HUMAN Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (By similarity). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (PubMed:29845874). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (PubMed:29845874).[UniProtKB:P51791]^[1] Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons.^[2]

Publication Abstract from PubMed

The trafficking and activity of endosomes relies on the exchange of chloride ions and protons by members of the CLC family of chloride channels and transporters, whose mutations are associated with numerous diseases. Despite their critical roles, the mechanisms by which CLC transporters are regulated are poorly understood. Here, we show that two related accessory beta-subunits, TMEM9 and TMEM9B, directly interact with ClC-3, -4 and -5. Cryo-EM structures reveal that TMEM9 inhibits ClC-3 by sealing the cytosolic entrance to the Cl(-) ion pathway. Unexpectedly, we find that PI(3,5)P(2) stabilizes the interaction between TMEM9 and ClC-3 and is required for proper regulation of ClC-3 by TMEM9. Collectively, our findings reveal that TMEM9 and PI(3,5)P(2) collaborate to regulate endosomal ion homeostasis by modulating the activity of ClC-3.

Structural basis of ClC-3 inhibition by TMEM9 and PI(3,5)P(2).,Schrecker M, Son Y, Planells-Cases R, Kar S, Vorobeva V, Schulte U, Fakler B, Jentsch TJ, Hite RK bioRxiv [Preprint]. 2025 Mar 3:2025.02.28.640562. doi: 10.1101/2025.02.28.640562. PMID:40093093^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jentsch TJ, Pusch M. CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease. Physiol Rev. 2018 Jul 1;98(3):1493-1590. PMID:29845874 doi:10.1152/physrev.00047.2017
↑ Ogura T, Furukawa T, Toyozaki T, Yamada K, Zheng YJ, Katayama Y, Nakaya H, Inagaki N. ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTR-regulated ORCC. FASEB J. 2002 Jun;16(8):863-5. PMID:11967229 doi:10.1096/fj.01-0845fje
↑ Schrecker M, Son Y, Planells-Cases R, Kar S, Vorobeva V, Schulte U, Fakler B, Jentsch TJ, Hite RK. Structural basis of ClC-3 inhibition by TMEM9 and PI(3,5)P(2). bioRxiv [Preprint]. 2025 Mar 3:2025.02.28.640562. PMID:40093093 doi:10.1101/2025.02.28.640562

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9dnx"

Categories: Homo sapiens | Large Structures | Hite RK | Schrecker M | Son Y

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[9dnx]] 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=9DNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DNX 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]] 2.86&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1A8I:[(2~{R})-1-octadecanoyloxy-3-[oxidanyl-[(2~{R},3~{R},5~{S},6~{R})-2,4,6-tris(oxidanyl)-3,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propan-2-yl]+(5~{E},11~{E},13~{E})-icosa-5,8,11,13-tetraenoate'>A1A8I</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1A8I:(2R)-1-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}-3-(octadecanoyloxy)propan-2-yl+(5E,8E,11E,13E)-icosa-5,8,11,13-tetraenoate'>A1A8I</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=9dnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dnx OCA], [https://pdbe.org/9dnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dnx RCSB], [https://www.ebi.ac.uk/pdbsum/9dnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dnx ProSAT]</span></td></tr>
 </table>

9dnx

From Proteopedia

Current revision

Human ClC-3:TMEM9, TMEM9 Protomer A and B: Complete

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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