Structural basis of aquaporin-4 autoantibody binding in neuromyelitis optica.

ABSTRACT: Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system where pathogenic autoantibodies target the water channel aquaporin-4 on human astrocytes 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 distinguis

SUBMITTER: Gupta M 

PROVIDER: S-EPMC11844742 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature