A lamin A/C beta-strand containing the site of lipodystrophy mutations is a major surface epitope for a new panel of monoclonal antibodies

• Published in: Biochimica et biophysica acta Vol. 1671; no. 1; pp. 87 - 92
• Main Authors: Manilal, Sushila, Randles, K.Natalie, Aunac, Christelle, Man, Nguyen thi, Morris, Glenn E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 17.03.2004
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - metabolism; Cells, Cultured; Emery–Dreifuss muscular dystrophy; Epitope Mapping; Epitopes; Fibroblasts - cytology; Fibroblasts - metabolism; Humans; Lamin Type A - genetics; Lamin Type A - immunology; Lamin Type A - metabolism; Lipodystrophy - genetics; Lipodystrophy - immunology; Models, Molecular; Molecular Sequence Data; Muscle, Skeletal - metabolism; Nuclear lamina; Peptide Library; Phage display; Protein Structure, Secondary; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; Sequence Alignment; Nuclear lamina; Epitope mapping; Phage display; Peptide library; Emery–Dreifuss muscular dystrophy
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2004.01.008

Using a phage-displayed peptide library, we have identified the epitope recognized by a new panel of five monoclonal antibodies (mAbs) raised against full-length recombinant human lamin A. The mAbs were found to recognize both lamin A and C by Western blotting and immunolocalization at the nuclear rim. A nine-amino acid consensus sequence PLLTYRFPP in the common immunoglobulin-like (Ig-like) domain of lamin A/C contains the binding site for all five mAbs. Three-dimensional structure of the Ig-like domain of lamin A/C shows this sequence is a complete beta-strand. This sequence includes arginine-482 (R482) which is mutated in most cases of Dunnigan-type familial partial lipodystrophy (FPLD). R482 may be part of an interaction site on the surface of lamin A/C for lamin-binding proteins associated with lipodystrophy.