9dnx | pdb_00009dnx

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

spinqualitylabelsall models 9dnx, resolution 2.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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: A1A8I, CL, CLR 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] Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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