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8VUR

Human GluN1-2A with IgG 003-102 WT conformation

Summary for 8VUR
Entry DOI10.2210/pdb8vur/pdb
EMDB information43537
DescriptorGlutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2A, 003-102 Heavy, ... (5 entities in total)
Functional Keywordschannel, heterotetramer, receptor, antibody, membrane protein-immune system complex, membrane protein/immune system
Biological sourceHomo sapiens (human)
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Total number of polymer chains6
Total formula weight413471.66
Authors
Michalski, K.,Furukawa, H. (deposition date: 2024-01-29, release date: 2024-09-11, Last modification date: 2024-11-06)
Primary citationMichalski, K.,Abdulla, T.,Kleeman, S.,Schmidl, L.,Gomez, R.,Simorowski, N.,Vallese, F.,Pruss, H.,Heckmann, M.,Geis, C.,Furukawa, H.
Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis.
Nat.Struct.Mol.Biol., 2024
Cited by
PubMed Abstract: 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.
PubMed: 39227719
DOI: 10.1038/s41594-024-01386-4
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.84 Å)
Structure validation

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PDB entries from 2024-11-20

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