The cellular functions of LEM proteins are not understood. LEM proteins are found in multicellular eukaryotes but not in single cell eukaryotes or plants ( Cohen et al., 2001). Collectively, these proteins are termed LEM ( LAP2- emerin- MAN1) proteins ( Lin et al., 2000). Within this constant region resides the so-called LEM motif ( Lin et al., 2000), which is also conserved in a growing number of other nuclear membrane proteins, including emerin and MAN1. All isoforms of LAP2 share a constant N-terminal region, encoded by exons 1–3 ( Berger et al., 1996), which spans residues 1–187 in the case of human LAP2 ( Harris et al., 1994). Lamin-associated polypeptide 2 (LAP2) comprises a family of alternatively spliced proteins that are associated with the inner nuclear membrane ( Foisner and Grace, 1993 Dechat et al., 2000a). Thus, LEM and LEM-like motifs form a common structure that evolution has customized for binding to BAF or DNA. Binding selectivity is determined by the nature of the surface residues in these binding sites, which are predominantly positively charged for LAP2-N and hydrophobic for the LEM-domain. Both binding surfaces comprise helix 1, the N-terminus of helix 2 and the inter-helical loop. NMR chemical shift mapping demonstrated that the LEM-domain binds BAF (barrier-to-autointegration factor), whereas LAP2-N binds DNA. This motif is shared by subdomains of T4 endonuclease VII and transcription factor rho, despite negligible (≤15%) sequence identity. The two domains are structurally homologous, comprising a helical turn followed by two helices connected by an 11–12-residue loop. Human LAP2 1–168 has two structurally independent, non-interacting domains located at residues 1–50 (‘LAP2-N’) and residues 111–152 (LEM-domain), connected by an ∼60-residue flexible linker. We have solved the solution NMR structure of the constant region of human LAP2 (residues 1–168). Loss of emerin causes Emery–Dreifuss muscular dystrophy. The nuclear envelope proteins LAP2, emerin and MAN1 share a conserved ∼40-residue ‘LEM’ motif.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |