Structure of a signaling-competent reelin fragment revealed by X-ray crystallography and electron tomography

Terukazu Nogi, Norihisa Yasui, Mitsuharu Hattori, Kenji Iwasaki, Junichi Takagi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 ∼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 Å crystal structure of the mouse reelin repeat 3 reveals that the subrepeat assumes a β-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.

Original languageEnglish
Pages (from-to)3675-3683
Number of pages9
JournalEMBO Journal
Volume25
Issue number15
DOIs
Publication statusPublished - Aug 9 2006
Externally publishedYes

Fingerprint

X Ray Tomography
Electron Microscope Tomography
X ray crystallography
X Ray Crystallography
Epidermal Growth Factor
Tomography
Phosphorylation
Tandem Repeat Sequences
Electrons
Neurons
Brain
Glycoproteins
Crystal structure
Carbohydrates
Molecules
Proteins
fibrinogen fragment X

Keywords

  • Brain development
  • Dab1
  • EGF module
  • Neuronal migration
  • Reelin

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Structure of a signaling-competent reelin fragment revealed by X-ray crystallography and electron tomography. / Nogi, Terukazu; Yasui, Norihisa; Hattori, Mitsuharu; Iwasaki, Kenji; Takagi, Junichi.

In: EMBO Journal, Vol. 25, No. 15, 09.08.2006, p. 3675-3683.

Research output: Contribution to journalArticle

Nogi, Terukazu ; Yasui, Norihisa ; Hattori, Mitsuharu ; Iwasaki, Kenji ; Takagi, Junichi. / Structure of a signaling-competent reelin fragment revealed by X-ray crystallography and electron tomography. In: EMBO Journal. 2006 ; Vol. 25, No. 15. pp. 3675-3683.
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