Structural analysis of emerin, an inner nuclear membrane protein mutated in X-linked Emery-Dreifuss muscular dystrophy

Like Duchenne and Becker muscular dystrophies, Emery-Dreifuss muscular dyst rophy (EDMD) is characterized by myopathic and cardiomyopathic abnormalitie s. EDMD has the particularity of being linked to mutations in nuclear prote ins. The X-linked form of EDMD is caused by mutations in the emerin gene, w hereas autosomal dominant EDMD is caused by mutations in the lamin A/C gene . Emerin colocalizes with lamin AIC in interphase cells, and binds in vitro to lamin A/C. Recent work suggests that lamin AIC might serve as a recepto r for emerin. We have undertaken a structural analysis of emerin, and in pa rticular of its N-terminal domain, which is comprised in the emerin segment critical for binding to lamin A/C. We show that re-ion 2-54 of emerin adop ts the LEM fold. This fold was originally described in the two N-terminal d omains of another inner nuclear membrane protein called lamina-associated p rotein 2 (LAP2). The existence of a conserved solvent-exposed surface on th e LEM domains of LAP2 and emerin is discussed, as well as the nature of a p ossible common target. (C) 2001 Federation of European Biochemical Societie s. Published by Elsevier Science B.V. All rights reserved.