Structural Basis for Specific Recognition of Reelin by Its Receptors

Norihisa Yasui, Terukazu Nogi, Junichi Takagi

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor, members of the low-density lipoprotein receptor (LDLR) protein family, function as neuronal receptors for a secreted glycoprotein reelin during brain development. In both receptors, the first LDLR class A (LA1) module is sufficient to bind reelin. Analysis of a 2.6 Å crystal structure of the reelin receptor-binding fragment in complex with the LA1 of ApoER2 revealed that Lys2467 of reelin is recognized by both a conserved Trp residue and calcium-coordinating acidic residues from LA1, which together with Lys2360 plays a critical role in the interaction. This "double-Lys" recognition mode is, in fact, shared among other LDLR family proteins in ligand binding. The interface between reelin and LA1 covers a small surface area of ∼350 Å2 on each side, which ensures a stable complex formation under physiological conditions. An examination of structure-guided mutagenesis on interface residues revealed key features of this interaction.

Original languageEnglish
Pages (from-to)320-331
Number of pages12
JournalStructure
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 10 2010
Externally publishedYes

Fingerprint

LDL Receptors
Mutagenesis
Glycoproteins
Proteins
Ligands
Calcium
Brain
reelin receptor
low density lipoprotein receptor-related protein 8

Keywords

  • CELLBIO
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Structural Basis for Specific Recognition of Reelin by Its Receptors. / Yasui, Norihisa; Nogi, Terukazu; Takagi, Junichi.

In: Structure, Vol. 18, No. 3, 10.03.2010, p. 320-331.

Research output: Contribution to journalArticle

Yasui, Norihisa ; Nogi, Terukazu ; Takagi, Junichi. / Structural Basis for Specific Recognition of Reelin by Its Receptors. In: Structure. 2010 ; Vol. 18, No. 3. pp. 320-331.
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