8hvt

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Structure of the human CLC-7/Ostm1 complex reveals a novel stateStructure of the human CLC-7/Ostm1 complex reveals a novel state

Structural highlights

8hvt 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 3.6Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CLCN7_HUMAN Albers-Schoenberg osteopetrosis;Autosomal recessive malignant osteopetrosis;Intermediate osteopetrosis. 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. The disease is caused by variants affecting the gene represented in this entry.

Function

CLCN7_HUMAN Slowly voltage-gated channel mediating the exchange of chloride ions against protons (PubMed:18449189, PubMed:21527911). Functions as antiporter and contributes to the acidification of the lysosome lumen and may be involved in maintaining lysosomal pH (PubMed:18449189, PubMed:21527911, PubMed:31155284). 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:P35523][1] [2] [3]

References

  1. Graves AR, Curran PK, Smith CL, Mindell JA. The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes. Nature. 2008 Jun 5;453(7196):788-92. PMID:18449189 doi:10.1038/nature06907
  2. Leisle L, Ludwig CF, Wagner FA, Jentsch TJ, Stauber T. ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity. EMBO J. 2011 Jun 1;30(11):2140-52. PMID:21527911 doi:10.1038/emboj.2011.137
  3. Nicoli ER, Weston MR, Hackbarth M, Becerril A, Larson A, Zein WM, Baker PR 2nd, Burke JD, Dorward H, Davids M, Huang Y, Adams DR, Zerfas PM, Chen D, Markello TC, Toro C, Wood T, Elliott G, Vu M, Zheng W, Garrett LJ, Tifft CJ, Gahl WA, Day-Salvatore DL, Mindell JA, Malicdan MCV. Lysosomal Storage and Albinism Due to Effects of a De Novo CLCN7 Variant on Lysosomal Acidification. Am J Hum Genet. 2019 Jun 6;104(6):1127-1138. PMID:31155284 doi:10.1016/j.ajhg.2019.04.008

8hvt, resolution 3.60Å

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OCA