Complex between nidogen and laminin fragments reveals a paradigmatic β-propeller interface
Complex between nidogen and laminin fragments reveals a paradigmatic β-propeller interface
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DOI：
10.1038/nature01873
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发表时间：
2003-08-21
期刊：
影响因子：
64.8
通讯作者：
Springer, TA
中科院分区：
文献类型：
--
作者：
Takagi, J;Yang, YT;Springer, TA
基底膜是所有后生动物组织结构和生理学的基础。层粘连蛋白和巢蛋白之间的相互作用对基底膜的组装至关重要（1-4）。相互作用结构域的结构揭示了巢蛋白中的六叶Tyr-Trp-Thr-Asp（YWTD）β-推进器结构域与层粘连蛋白中的层粘连蛋白表皮生长因子样（LE）模块III 3 -5（LE 3 -5）结合。层粘连蛋白LE模块4结合到β-螺旋桨的伪6倍轴上的圆形剧场形表面，LE模块3结合在其边缘上。关闭β-螺旋桨的充满水的中心孔的Phe残基、圆形剧场的刚性和高度的形状互补性使得能够构建进化上保守的LE 4结合表面，该结合表面对于其小尺寸具有前所未有的高亲和力（5）。Wnt共受体LRP 5中的超形态突变（参考文献6-9）表明，类似的YWTD β-螺旋桨界面用于结合在发育途径中起作用的配体。在低密度脂蛋白受体中使用了一个相关的界面，但偏离了伪6重轴的中心，并且在中心孔上没有快门，用于分子内相互作用，该相互作用在受体再循环中受pH值调节（10）。
Basement membranes are fundamental to tissue organization and physiology in all metazoans. The interaction between laminin and nidogen is crucial to the assembly of basement membranes(1-4). The structure of the interacting domains reveals a six-bladed Tyr-Trp-Thr-Asp (YWTD) beta-propeller domain in nidogen bound to laminin epidermal-growth-factor-like (LE) modules III3-5 in laminin (LE3-5). Laminin LE module 4 binds to an amphitheatre-shaped surface on the pseudo-6-fold axis of the beta-propeller, and LE module 3 binds over its rim. A Phe residue that shutters the water-filled central aperture of the beta-propeller, the rigidity of the amphitheatre, and high shape complementarity enable the construction of an evolutionarily conserved binding surface for LE4 of unprecedentedly high affinity for its small size(5). Hypermorphic mutations in the Wnt co-receptor LRP5 (refs 6-9) suggest that a similar YWTD beta-propeller interface is used to bind ligands that function in developmental pathways. A related interface, but shifted off-centre from the pseudo-6-fold axis and lacking the shutter over the central aperture, is used in the low-density lipoprotein receptor for an intramolecular interaction that is regulated by pH in receptor recycling(10).