Structural characterization of the LEM motif common to three human inner nuclear membrane proteins.
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.
Laguri
C
C
Département d'Ingénierie et d'Etudes des Protéines, CEA Saclay, 91191, Gif-sur-Yvette, France.
Gilquin
B
B
Wolff
N
N
Romi-Lebrun
R
R
Courchay
K
K
Callebaut
I
I
Worman
H J
HJ
Zinn-Justin
S
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001704:Biopolymers; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D001704:Biopolymers; D008565:Membrane Proteins