{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Gupta M"],"funding":["NEI NIH HHS","NIA NIH HHS","NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["Neuromyelitis Optica (NMO) is an autoimmune disease of the central nervous system where pathogenic autoantibodies target the human astrocyte water channel aquaporin-4 causing neurological impairment. Autoantibody binding leads to complement dependent and complement independent cytotoxicity, ultimately resulting in astrocyte death, demyelination, and neuronal loss. Aquaporin-4 assembles in astrocyte plasma membranes as symmetric tetramers or as arrays of tetramers. We report molecular structures of aquaporin-4 alone and bound to Fab fragments from patient-derived NMO autoantibodies using cryogenic electron microscopy. Each antibody binds to epitopes comprised of three extracellular loops of aquaporin-4 with contributions from multiple molecules in the assembly. The structures distinguish between antibodies that bind to the tetrameric form of aquaporin-4, and those targeting higher order orthogonal arrays of tetramers that provide more diverse bridging epitopes."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.05.12.592631"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11118524"],"repository":["biostudies-literature"],"pubmed_title":["Structural Basis of Aquaporin-4 Autoantibody Binding in Neuromyelitis Optica."],"pmcid":["PMC11118524"],"funding_grant_id":["K99 AG070271","S10 OD020054","S10 OD026881","R01 GM024485","R01 EY022936","S10 OD021741"],"pubmed_authors":["Hwang P","Stroud RM","Nelson A","Pourmal S","Khandelwal NK","Gupta M","Bennett JL"],"additional_accession":[]},"is_claimable":false,"name":"Structural Basis of Aquaporin-4 Autoantibody Binding in Neuromyelitis Optica.","description":"Neuromyelitis Optica (NMO) is an autoimmune disease of the central nervous system where pathogenic autoantibodies target the human astrocyte water channel aquaporin-4 causing neurological impairment. Autoantibody binding leads to complement dependent and complement independent cytotoxicity, ultimately resulting in astrocyte death, demyelination, and neuronal loss. Aquaporin-4 assembles in astrocyte plasma membranes as symmetric tetramers or as arrays of tetramers. We report molecular structures of aquaporin-4 alone and bound to Fab fragments from patient-derived NMO autoantibodies using cryogenic electron microscopy. Each antibody binds to epitopes comprised of three extracellular loops of aquaporin-4 with contributions from multiple molecules in the assembly. The structures distinguish between antibodies that bind to the tetrameric form of aquaporin-4, and those targeting higher order orthogonal arrays of tetramers that provide more diverse bridging epitopes.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-04-13T03:27:11.995Z","creation":"2026-04-13T03:12:59.499Z"},"accession":"S-EPMC11118524","cross_references":{"pubmed":["38798537"],"doi":["10.1101/2024.05.12.592631"]}}