2026-06-07T04:18:35Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1080522025-03-18T12:54:41Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Michalski, Kevin author Abdulla, Taha author Kleeman, Sam author Schmidl, Lars author Gómez García, Ricardo author Simorowski, Noriko author Vallese, Francesca author Prüss, Harald author Heckmann, Manfred author Geis, Christian author Furukawa, Hiro 2024-09-10T10:32:32Z 2024-09-10T10:32:32Z 2024-09-03 Michalski, K., Abdulla, T., Kleeman, S. et al. Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis. Nat Struct Mol Biol (2024). https://doi.org/10.1038/s41594-024-01386-4 1545-9993 10.1038/s41594-024-01386-4 https://hdl.handle.net/20.500.14352/108052 1545-9985 https://doi.org/10.1038/s41594-024-01386-4 https://www.nature.com/articles/s41594-024-01386-4 Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most dominant autoimmune encephalitis; however, insights into how autoantibodies recognize and alter receptor functions remain limited. Here we determined structures of human and rat NMDARs bound to three distinct patient-derived antibodies using single-particle electron cryo-microscopy. These antibodies bind different regions within the amino-terminal domain of the GluN1 subunit. Through electrophysiology, we show that all three autoantibodies acutely and directly reduced NMDAR channel functions in primary neurons. Antibodies show different stoichiometry of binding and antibody–receptor complex formation, which in one antibody, 003-102, also results in reduced synaptic localization of NMDARs. These studies demonstrate mechanisms of diverse epitope recognition and direct channel regulation of anti-NMDAR autoantibodies underlying autoimmune encephalitis. eng Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis journal article 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