Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain.
Neurofibromatosis type 2 (NF2) is a dominantly inherited disease associated with the central nervous system. The NF2 gene product merlin is a tumor suppressor, and its mutation or inactivation causes this disease. We report here the crystal structure of the merlin FERM domain containing a 22-residue alpha-helical segment. The structure reveals that the merlin FERM domain consists of three subdomains displaying notable features of the electrostatic surface potentials, although the overall surface potentials similar to those of ezrin/radixin/moesin (ERM) proteins indicate electrostatic membrane association. The structure also is consistent with inactivation mechanisms caused by the pathogenic mutations associated with NF2.
Shimizu
Toshiyuki
T
Structural Biology Laboratory, Nara Institute of Science and Technology and CREST, Japan.
Seto
Azusa
A
Maita
Nobuo
N
Hamada
Keisuke
K
Tsukita
Shoichiro
S
Tsukita
Sachiko
S
Hakoshima
Toshio
T
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016518:Neurofibromatosis 2 / Q000235:genetics* / Q000378:metabolism*; D025581:Neurofibromin 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D025581:Neurofibromin 2