Structure of the F-spondin reeler domain reveals a unique β-sandwich fold with a deformable disulfide-bonded loop
Structure of the F-spondin reeler domain reveals a unique β-sandwich fold with a deformable disulfide-bonded loop
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DOI：
10.1107/s0907444908028308
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发表时间：
2008-11-01
影响因子：
2.2
通讯作者：
Takagi, Junichi
中科院分区：
文献类型：
--
作者：
Nagae, Masamichi;Nishikawa, Ken;Takagi, Junichi
F-spondin是一种分泌的细胞外基质附着蛋白，在神经发育过程中参与轴突寻路以及成人组织中的血管重塑。F-spondin由一个reeler、一个spondin和六个1型血小板反应蛋白重复结构域组成。reeler结构域与reelin的氨基末端结构域共享同源性，reelin是一种在皮质发育期间引导迁移神经元的大分泌糖蛋白。在1.45和2.70 A分辨率下测定F-脊椎蛋白卷轴结构域的晶体结构。该结构揭示了一个九链的反平行β-夹心折叠类似于免疫球蛋白或纤连蛋白III型结构域，但具有独特的额外β-发夹。此外，在其开始时通过保守的二硫键锚定的氨基末端延伸松散地包装在β-夹心的一面上，对结构域的表面特征做出了主要贡献。两种不同晶体中所含的不同分子之间的结构比较揭示了氨基末端环的不寻常的构象可塑性，表明其在分子相互作用中的作用。
F-spondin is a secreted and extracellular matrix-attached protein that has been implicated in axonal pathfinding during neural development as well as in vascular remodelling in adult tissues. F-spondin is composed of a reeler, a spondin and six thrombospondin type 1 repeat domains. The reeler domain shares homology with the amino-terminal domain of reelin, a large secreted glycoprotein that guides migrating neurons during cortical development. Crystal structures of the F-spondin reeler domain were determined at 1.45 and 2.70 A resolution. The structure revealed a nine-stranded antiparallel beta-sandwich fold similar to the immunoglobulin or fibronectin type III domains, but with a unique extra beta-hairpin. Moreover, an amino-terminal extension which is anchored at its beginning via a conserved disulfide bond loosely packs against one face of the beta-sandwich, making a major contribution to the surface features of the domain. Structural comparison among the different molecules contained in two different crystals reveals an unusual conformational plasticity of the amino-terminal loop, suggesting its role in molecular interactions.