Journal
SCIENCE ADVANCES
Volume 6, Issue 33, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb4747
Keywords
-
Categories
Funding
- National Key R&D Program of China [2017YFA0504600, 2016YFA0501100, 2018ZX09711002]
- Fundamental Research Funds for the Central Universities [22120180534]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12040220]
- National Science Fund for Distinguished Young Scholars [31625008]
- National Natural Science Foundation of China [21532004, 31570733, 81771188, 81901376, 31671049]
Ask authors/readers for more resources
CLC family proteins translocate chloride ions across cell membranes to maintain the membrane potential, regulate the transepithelial Cl- transport, and control the intravesicular pH among different organelles. CLC-7/Ostm1 is an electrogenic Cl-/H+ antiporter that mainly resides in lysosomes and osteoclast ruffled membranes. Mutations in human CLC-7/Ostm1 lead to lysosomal storage disorders and severe osteopetrosis. Here, we present the cryoelectron microscopy (cryo-EM) structure of the human CLC-7/Ostm1 complex and reveal that the highly glycosylated Ostm1 functions like a lid positioned above CLC-7 and interacts extensively with CLC-7 within the membrane. Our complex structure reveals a functionally crucial domain interface between the amino terminus, TMD, and CBS domains of CLC-7. Structural analyses and electrophysiology studies suggest that the domain interaction interfaces affect the slow gating kinetics of CLC-7/Ostm1. Thus, our study deepens understanding of CLC-7/Ostm1 transporter and provides insights into the molecular basis of the disease-related mutations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available