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TitleCryo-EM structure of the lysosomal chloride-proton exchanger CLC-7 in complex with OSTM1.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateAug 4, 2020
AuthorsMarina Schrecker / Julia Korobenko / Richard K Hite /
PubMed AbstractThe chloride-proton exchanger CLC-7 plays critical roles in lysosomal homeostasis and bone regeneration and its mutation can lead to osteopetrosis, lysosomal storage disease and neurological ...The chloride-proton exchanger CLC-7 plays critical roles in lysosomal homeostasis and bone regeneration and its mutation can lead to osteopetrosis, lysosomal storage disease and neurological disorders. In lysosomes and the ruffled border of osteoclasts, CLC-7 requires a β-subunit, OSTM1, for stability and activity. Here, we present electron cryomicroscopy structures of CLC-7 in occluded states by itself and in complex with OSTM1, determined at resolutions up to 2.8 Å. In the complex, the luminal surface of CLC-7 is entirely covered by a dimer of the heavily glycosylated and disulfide-bonded OSTM1, which serves to protect CLC-7 from the degradative environment of the lysosomal lumen. OSTM1 binding does not induce large-scale rearrangements of CLC-7, but does have minor effects on the conformation of the ion-conduction pathway, potentially contributing to its regulatory role. These studies provide insights into the role of OSTM1 and serve as a foundation for understanding the mechanisms of CLC-7 regulation.
External linksElife / PubMed:32749217 / PubMed Central
MethodsEM (single particle)
Resolution2.82 - 2.92 Å
Structure data

22386

7jm6

EMDB-22386, PDB-7jm6:
Structure of chicken CLC-7
Method: EM (single particle) / Resolution: 2.92 Å

22389

7jm7

EMDB-22389, PDB-7jm7:
Structure of human CLC-7/OSTM1 complex
Method: EM (single particle) / Resolution: 2.82 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-CL:
Unknown entry

ChemComp-0J1:
(2R)-3-{[(R)-hydroxy{[(1S,2R,3S,4S,5R,6R)-2,3,4,6-tetrahydroxy-5-(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dinonanoate

ChemComp-HOH:
WATER

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • gallus gallus (chicken)
  • Homo (humans)
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Lysosomal / chloride-proton antiporter / chloride transport / ion transport / proton transport / complex / glycosylated

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