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

Mengli Cai, Ying Huang, Rodolfo Ghirlando, Katherine L. Wilson, Robert Craigie, G. Marius Clore

Research output: Contribution to journalArticlepeer-review

Abstract

The nuclear envelope proteins LAP2, emerin and MAN1 share a conserved ∼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 LAP21-168 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. 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 sub-domains of T4 endonuclease VII and transcription factor rho, despite negligible (≤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.

Original languageEnglish (US)
Pages (from-to)4399-4407
Number of pages9
JournalEMBO Journal
Volume20
Issue number16
DOIs
StatePublished - Aug 15 2001

Keywords

  • LAP2
  • LEM motif
  • NMR
  • Structure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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