Fig. 1

Lamin structure. A schematic sketch of a generic lamin protein, highlighting the important structural features. The N-terminal head domain is short and mostly unstructured, and also contains a conserved phosphorylation site flanking the rod domain, which is important for lamin polymer disassembly and reassembly during mitosis. Another phosphorylation site is situated at the other extremity of the rod domain. The central rod domain is mainly composed of α-helices, consisting of four coiled coils, interrupted by flexible linker domains. The rod domain is essential for the dimerization of lamin, which is the first step required for the assembly of lamin filaments. The C-terminal tail domain of lamin protein includes a structured immunoglobulin-like domain, structurally well conserved among species, as well as the evolutionarily conserved nuclear localization signal (NLS) and CaaX motifs ("C" stands for cysteine, "a" any aliphatic amino acid, and the identity of "X" determines the enzyme that acts on the protein). In lamin the motif is recognized by a farnesyltransferase. Arrows under the sketch indicate the position of the two EDMD causing mutations on the lamin protein discussed in the review, and of the most common HGPS (progeria) mutation G608G. Δ32K in mice corresponds to the deletion of the lysine 32, which corresponds to Δ46K in C. elegans. Y59C is a missense mutation at the beginning of the rod domain in C. elegans lamin, analogous to the 45C mutation in human lamin A/C. The hundreds of other mutations leading to laminopathies are spread almost all over the lamin protein [151]