Structure of a signaling-competent reelin fragment revealed by X-ray crystallography and electron tomography.
The large extracellular glycoprotein reelin directs neuronal migration during brain development and plays a fundamental role in layer formation. It is composed of eight tandem repeats of an approximately 380-residue unit, termed the reelin repeat, which has a central epidermal growth factor (EGF) module flanked by two homologous subrepeats with no obvious sequence similarity to proteins of known structure. The 2.05 A crystal structure of the mouse reelin repeat 3 reveals that the subrepeat assumes a beta-jelly-roll fold with unexpected structural similarity to carbohydrate-binding domains. Despite the interruption by the EGF module, the two subdomains make direct contact, resulting in a compact overall structure. Electron micrographs of a four-domain fragment encompassing repeats 3-6, which is capable of inducing Disabled-1 phosphorylation in neurons, show a rod-like shape. Furthermore, a three-dimensional molecular envelope of the fragment obtained by single-particle tomography can be fitted with four concatenated repeat 3 atomic structures, providing the first glimpse of the structural unit for this important signaling molecule.
Nogi
Terukazu
T
Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
Yasui
Norihisa
N
Hattori
Mitsuharu
M
Iwasaki
Kenji
K
Takagi
Junichi
J
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron / Q000379:methods; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D000091042:Reelin Protein; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014054:Tomography / Q000379:methods
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases