title: A lamin A/C beta-strand containing the site of lipodystrophy mutations is a major surface epitope for a new panel of monoclonal antibodies.
abstract: 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.
authors.affiliation: MRIC Biochemistry Group, North East Wales Institute, Mold Road, Wrexham, LL11 2AW, UK.
authors.forename: Sushila
authors.initials: S
authors.lastname: Manilal
authors.forename: K Natalie
authors.initials: KN
authors.lastname: Randles
authors.forename: Christelle
authors.initials: C
authors.lastname: Aunac
authors.forename: Man thi
authors.initials: Mt
authors.lastname: Nguyen
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Morris
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018604:Epitope Mapping; D000939:Epitopes; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D008060:Lipodystrophy / Q000235:genetics* / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D019151:Peptide Library; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D034904:Lamin Type A; D019151:Peptide Library; D011994:Recombinant Proteins; C440308:lamin C