Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA

EMBO J. 2001 Aug 15;20(16):4399-407. doi: 10.1093/emboj/20.16.4399.


The nuclear envelope proteins LAP2, emerin and MAN1 share a conserved approximately 40-residue 'LEM' motif. Loss of emerin causes Emery-Dreifuss muscular dystrophy. We have solved the solution NMR structure of the constant region of human LAP2 (residues 1-168). 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 approximately 60-residue flexible linker. The two domains are structurally homologous, comprising a helical turn followed by two helices connected by an 11-12-residue loop. This motif is shared by subdomains of T4 endonuclease VII and transcription factor rho, despite negligible (< or =15%) sequence identity. NMR chemical shift mapping demonstrated that the LEM-domain binds BAF (barrier-to-autointegration factor), whereas LAP2-N binds DNA. Both binding surfaces comprise helix 1, the N-terminus of helix 2 and the inter-helical loop. 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. Thus, LEM and LEM-like motifs form a common structure that evolution has customized for binding to BAF or DNA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • DNA / chemistry
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Envelope / metabolism
  • Nuclear Proteins*
  • Nucleoproteins / metabolism
  • Protein Structure, Tertiary
  • Solutions


  • BANF1 protein, human
  • DNA-Binding Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Nucleoproteins
  • Solutions
  • lamina-associated polypeptide 2
  • DNA

Associated data

  • PDB/1GJJ