Nuclear lamins and the nucleoskeleton

Abstract

Sequence comparison, as well as structural analysis, has classified lamins as intermediate filament (IF) proteins. Lamins show the structural features diagnostic for members of the IF protein family. This sequence principle is responsible for the coiled-coil forming ability of IF proteins. Sequence similarity within the lamin subfamily is high, reaching values of 60% to 80% amino acid identity among members of the vertebrate lamins. Sequence similarity between cytoplasmic IFs and nuclear lamins, on the other hand, is seen only at the ends of the rod domains. The central rod domain of lamins is about 360 amino acids long, and alignment of the lamin rod sequences can be done without introducing any gap. The tail domain of nuclear lamins have two hallmark sequences by which lamins are distinguished from cytoplasmic IF proteins and that are related to lamin functionality. These are a nuclear localization signal and a C-terminal CaaX motif. These two topogenic sequences are necessary for targeting newly synthesized lamins to the inner nuclear envelope membrane.