Atomic Structures of Two Novel Immunoglobulin-like Domain Pairs in the Actin Cross-linking Protein Filamin
Atomic Structures of Two Novel Immunoglobulin-like Domain Pairs in the Actin Cross-linking Protein Filamin
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DOI：
10.1074/jbc.m109.019661
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发表时间：
2009-09-11
影响因子：
4.8
通讯作者：
Ylanne, Jari
中科院分区：
文献类型：
--
作者：
Heikkinen, Outi K.;Ruskamo, Salla;Ylanne, Jari
丝状蛋白是肌动蛋白丝交联蛋白，由N-末端肌动蛋白结合结构域和24个免疫球蛋白样结构域（IgFLN）组成。丝状体与许多蛋白质相互作用，包括质膜信号传导和细胞粘附受体的胞质结构域。从而将细胞膜机械地和功能性地连接到细胞骨架。大多数相互作用已被映射到C-末端IgFLN 16-24。类似地，与先前已知的IgFLNa 20 -21的紧凑结构域对一样，双结构域片段IgFLNa 16 -17和IgFLNa 18 -19在小角X射线散射分析中比两个独立结构域预期的更紧凑。溶液状态NMR结构显示IgFLNa 18 -19中的结构域堆积类似于IgFLNa 20 -21的结构。在这两个结构域对的整合素结合位点被掩盖，虽然结构域的相互作用的细节是部分不同的。IgFLNa 16 -17的结构揭示了一种新的结构域包装模式，其中结构域17的粘附受体结合位点未被掩蔽。序列比较表明，类似的包装的三个串联细丝蛋白结构域对是存在于整个动物王国，我们建议，这种包装是通过机械传感器机制参与细丝蛋白相互作用的调节。
Filamins are actin filament cross-linking proteins composed of an N-terminal actin-binding domain and 24 immunoglobulin-like domains (IgFLNs). Filamins interact with numerous proteins, including the cytoplasmic domains of plasma membrane signaling and cell adhesion receptors. Thereby filamins mechanically and functionally link the cell membrane to the cytoskeleton. Most of the interactions have been mapped to the C-terminal IgFLNs 16-24. Similarly, as with the previously known compact domain pair of IgFLNa20-21, the two-domain fragments IgFLNa16-17 and IgFLNa18-19 were more compact in small angle x-ray scattering analysis than would be expected for two independent domains. Solution state NMR structures revealed that the domain packing in IgFLNa18-19 resembles the structure of IgFLNa20-21. In both domain pairs the integrin-binding site is masked, although the details of the domain-domain interaction are partly distinct. The structure of IgFLNa16-17 revealed a new domain packing mode where the adhesion receptor binding site of domain 17 is not masked. Sequence comparison suggests that similar packing of three tandem filamin domain pairs is present throughout the animal kingdom, and we propose that this packing is involved in the regulation of filamin interactions through a mechanosensor mechanism.