Figure 3.

The LMNB2 mutation causes an amino acid change in a highly conserved domain of lamin B₂. (A) Sequence chromatograms showing the wild-type sequence (upper line) and the c.469C>T (p.His157Tyr) mutation (lower line). The mutated nucleotide is marked in red. (B) Amino acid sequence alignment of the center eight heptads of coil 1B of lamin B₂ for members of three different vertebrate classes: human (H. sapiens, accession NM_032737.3), chicken (G. gallus, accession NM_205285.1) and frog (X. laevis, accession NM_001087478.1). Identical amino acids are highlighted in turquois, positions where two amino acids are identical and the third is of homologous character are highlighted in yellow. Positions of the heptad repeat, mediating coiled-coil formation of a-helices, are indicated below the amino acid sequences. For the organization of subdomains in lamins, see (13,35) and references therein. The H157 residue is conserved from frog to man in an overall highly conserved segment of two and a half heptads. Note that through the introduction of a tyrosine in this position, two consecutive bulky aromatic residues are found in an a- and b-position, which is unfavorable for the stability of a coiled coil.