7bxu

CLC-7/Ostm1 membrane protein complex

spinqualitylabelsall models 7bxu, resolution 3.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7bxu 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 3.7Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease OSTM1_HUMAN Infantile osteopetrosis with neuroaxonal dysplasia. The disease is caused by variants affecting the gene represented in this entry. Function OSTM1_HUMAN Required for osteoclast and melanocyte maturation and function. Publication Abstract from PubMed 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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