Download MendeleyStructural Basis for Specific Recognition of Reelin by Its Receptors
Yasui, N., Nogi, T., Takagi, J.(2010) Structure 18: 320-331
- PubMed: 20223215
- DOI: https://doi.org/10.1016/j.str.2010.01.010
- Primary Citation of Related Structures:
3A7Q - PubMed 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 A 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 approximately 350 A(2) 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.
Organizational Affiliation:
Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
