{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:17:26Z","timestamp":1792736246404,"version":"4.5.0"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"8","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,2,21]]},"abstract":"<jats:p>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 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.<\/jats:p>","DOI":"10.1126\/sciadv.adq7560","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:00:26Z","timestamp":1740146426000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Structural basis of aquaporin-4 autoantibody binding in neuromyelitis optica"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7432-3211","authenticated-orcid":true,"given":"Meghna","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA."},{"name":"Department of Chemical Physiology and Biochemistry, Oregon Health &amp; Science University, Portland, OR 97239, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitesh Kumar","family":"Khandelwal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA."},{"name":"Department of Chemical Physiology and Biochemistry, Oregon Health &amp; 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