Reelin 与其受体特异性识别的结构基础。

Structural basis for specific recognition of reelin by its receptors.

机构信息

Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.

出版信息

Structure. 2010 Mar 10;18(3):320-31. doi: 10.1016/j.str.2010.01.010.

DOI:10.1016/j.str.2010.01.010

PMID:20223215

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.

摘要

载脂蛋白 E 受体 2（ApoER2）和极低密度脂蛋白受体是 LDLR 蛋白家族的成员，在脑发育过程中作为一种分泌糖蛋白 Reelin 的神经元受体发挥作用。在这两种受体中，第一个 LDLR 类 A（LA1）模块足以结合 Reelin。对 Reelin 受体结合片段与 ApoER2 的 LA1 复合物的 2.6Å 晶体结构分析表明，Reelin 的 Lys2467 被一个保守的色氨酸残基和 LA1 中的钙配位酸性残基识别，Lys2360 与该残基共同在相互作用中发挥关键作用。这种“双-Lys”识别模式实际上在配体结合的其他 LDLR 家族蛋白中共享。Reelin 和 LA1 之间的界面在每一侧覆盖约 350Å2 的小表面积，这确保了在生理条件下稳定的复合物形成。对界面残基的结构指导诱变的检查揭示了这种相互作用的关键特征。