Structural characterization of the LEM motif common to three human inner nuclear membrane proteins

Structure. 2001 Jun;9(6):503-11. doi: 10.1016/s0969-2126(01)00611-6.

Abstract

Background: Integral membrane proteins of the inner nuclear membrane are involved in chromatin organization and postmitotic reassembly of the nucleus. The discovery that mutations in the gene encoding emerin causes X-linked Emery-Dreifuss muscular dystrophy has enhanced interest in such proteins. A common structural domain of 50 residues, called the LEM domain, has been identified in emerin MAN1, and lamina-associated polypeptide (LAP) 2. In particular, all LAP2 isoforms share an N-terminal segment composed of such a LEM domain that is connected to a highly divergent LEM-like domain by a linker that is probably unstructured.

Results: We have determined the three-dimensional structures of the LEM and LEM-like domains of LAP2 using nuclear magnetic resonance and molecular modeling. Both domains adopt the same fold, mainly composed of two large parallel alpha helices.

Conclusions: The structural LEM motif is found in human inner nuclear membrane proteins and in protein-protein interaction domains from bacterial multienzyme complexes. This suggests that LEM and LEM-like domains are protein-protein interaction domains. A region conserved in all LEM domains, at the surface of helix 2, could mediate interaction between LEM domains and a common protein partner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs*
  • Amino Acid Sequence
  • Biopolymers
  • Humans
  • Membrane Proteins / chemistry*
  • Molecular Sequence Data
  • Nuclear Envelope / chemistry*
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Static Electricity

Substances

  • Biopolymers
  • Membrane Proteins

Associated data

  • PDB/1H9E
  • PDB/1H9F