7BXU

CLC-7/Ostm1 membrane protein complex

Summary for 7BXU

• Entry DOI: 10.2210/pdb7bxu/pdb
• EMDB information: 30238
• Descriptor: Osteopetrosis-associated transmembrane protein 1, H(+)/Cl(-) exchange transporter 7, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: complex, lysosome, transporter, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 255225.80

Authors

Zhang, S.S.,Yang, M.J. (deposition date: 2020-04-20, release date: 2020-09-16, Last modification date: 2024-10-16)

Primary citation

Zhang, S.,Liu, Y.,Zhang, B.,Zhou, J.,Li, T.,Liu, Z.,Li, Y.,Yang, M.
Molecular insights into the human CLC-7/Ostm1 transporter.
Sci Adv, 6:eabb4747-eabb4747, 2020

PubMed Abstract: 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.

PubMed: 32851177
DOI: 10.1126/sciadv.abb4747

Experimental method

ELECTRON MICROSCOPY (3.7 Å)