Structural mechanisms of GABA_A receptor autoimmune encephalitis.

ABSTRACT: Autoantibodies targeting neuronal membrane proteins can cause encephalitis, seizures, and severe behavioral abnormalities. While antibodies for several neuronal targets have been identified, structural details on how they regulate function are unknown. Here we determined cryo-electron microscopy structures of antibodies derived from an encephalitis patient bound to the γ-aminobutyric acid type A (GABA_A) receptor. These antibodies induced severe encephalitis by directly inhibiting GABA_A function, resulting in nervous-system hyperexcitability. The structures reveal mechanisms of GABA_A inhibition and pathology. One antibody directly competes with a neurotransmitter and locks the receptor in a resting-like state. The second antibody targets the subunit interfac

SUBMITTER: Noviello CM 

PROVIDER: S-EPMC9394431 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature