7bxu | pdb_00007bxu
CLC-7/Ostm1 membrane protein complex
Structural highlights
DiseaseOSTM1_HUMAN Infantile osteopetrosis with neuroaxonal dysplasia. The disease is caused by variants affecting the gene represented in this entry. FunctionOSTM1_HUMAN Required for osteoclast and melanocyte maturation and function.[1] Publication Abstract from PubMedCLC 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 cryo-electron 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. Molecular insights into the human CLC-7/Ostm1 transporter.,Zhang S, Liu Y, Zhang B, Zhou J, Li T, Liu Z, Li Y, Yang M Sci Adv. 2020 Aug 12;6(33):eabb4747. doi: 10.1126/sciadv.abb4747. eCollection, 2020 Aug. PMID:32851177[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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