Congenital myasthenic syndromes and myasthenia

Mechanistic analyses of CMS caused by mutations in acetylcholine receptor (AChR) have guided therapy and yielded insights into structure-function relationships. AChR is a Cys-loop receptor formed by two α, and one β, δ and ε subunits surrounding an ion channel whose opening is triggered by agonist binding to α/δ and α/ε binding sites. A principal pathway that transduces agonist binding to channel opening was identified in the α-subunit: an invariant Arg residue (αR209) in the pre-M1 domai n couples with three nearby negatively charged residues (αE45, αE175, and αE138) in different loops extending to the ligand binding site.

Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: X. Shen, D. Selcen, J. Brengman, S. Shen, H. Durmus, V. Preethish-Kumar, A. Yuceyar, S. Vengalil, A. Nalini, F. Deymeer, S. Sine, A. Engel Source Type: research