Novel Functional Properties of Missense Mutations in the Glycine Receptor β Subunit in Startle Disease.

ABSTRACT: Startle disease is a rare disorder associated with mutations in GLRA1 and GLRB, encoding glycine receptor (GlyR) α1 and β subunits, which enable fast synaptic inhibitory transmission in the spinal cord and brainstem. The GlyR β subunit is important for synaptic localization via interactions with gephyrin and contributes to agonist binding and ion channel conductance. Here, we have studied three GLRB missense mutations, Y252S, S321F, and A455P, identified in startle disease patients. For Y252S in M1 a disrupted stacking interaction with surrounding aromatic residues in M3 and M4 is suggested which is accompanied by an increased EC₅₀ value. By contrast, S321F in M3 might stabilize stacking interactions with aromatic residues in M1 and M4. No significant differ

SUBMITTER: Piro I 

PROVIDER: S-EPMC8498107 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature