Separation of Coiled-Coil Structures in Lamin A/C Is Required for the Elongation of the Filament
Jinsook Ahn,
Soyeon Jeong,
So-Mi Kang,
Inseong Jo,
Bum-Joon Park,
Nam-Chul Ha
Affiliations
Jinsook Ahn
Department of Agricultural Biotechnology, Centre for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University, Seoul 08826, Korea
Soyeon Jeong
Department of Agricultural Biotechnology, Centre for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University, Seoul 08826, Korea
So-Mi Kang
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 46241, Korea
Inseong Jo
Department of Agricultural Biotechnology, Centre for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University, Seoul 08826, Korea
Bum-Joon Park
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 46241, Korea
Nam-Chul Ha
Department of Agricultural Biotechnology, Centre for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University, Seoul 08826, Korea
Intermediate filaments (IFs) commonly have structural elements of a central α-helical coiled-coil domain consisting of coil 1a, coil 1b, coil 2, and their flanking linkers. Recently, the crystal structure of a long lamin A/C fragment was determined and showed detailed features of a tetrameric unit. The structure further suggested a new binding mode between tetramers, designated eA22, where a parallel overlap of coil 1a and coil 2 is the critical interaction. This study investigated the biochemical effects of genetic mutations causing human diseases, focusing on the eA22 interaction. The mutant proteins exhibited either weakened or augmented interactions between coil 1a and coil 2. The ensuing biochemical results indicated that the interaction requires the separation of the coiled-coils in the N-terminal of coil 1a and the C-terminal of coil 2, coupled with the structural transition in the central α-helical rod domain. This study provides insight into the role of coil 1a as a molecular regulator in the elongation of IF proteins.
