Structural basis of diverse sequence-dependent target recognition by the 8 kDa dynein light chain
Structural basis of diverse sequence-dependent target recognition by the 8 kDa dynein light chain
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DOI：
10.1006/jmbi.2000.4374
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发表时间：
2001-02-09
影响因子：
5.6
通讯作者：
Zhang, MJ
中科院分区：
文献类型：
--
作者：
Fan, JS;Zhang, Q;Zhang, MJ
动力蛋白是一种多亚基的分子马达，可使分子货物沿沿着转运。除了作为动力蛋白运动复合体的重要组成部分，动力蛋白轻链的89个残基亚基（DLC 8）还通过与各种蛋白质和酶结合来调节许多其他生物事件。目前已知的DLC 8靶点包括神经元型一氧化氮合酶;称为Bim的促凋亡Bcl-2家族成员蛋白;果蝇RNA定位蛋白Swallow、肌球蛋白V、神经元支架蛋白GKAP和NF κ B转录因子抑制剂I κ B α。各种靶标的DLC 8结合结构域被限制在氨基酸残基的短的连续延伸内。然而，这些结构域彼此不共享任何明显的序列同源性。在这里，DLC 8的三维结构与对应于DLC 8结合结构域的神经元型一氧化氮合酶和Bim，分别两个肽复合，通过NMR光谱测定。虽然两种DLC 8结合肽具有完全不同的氨基酸序列，但两种肽通过经由蛋白质的β 2链通过反平行α-折叠扩增接合对称DLC 8二聚体而以显著相似的构象结合蛋白质。结构比较表明，这两个目标肽使用不同的区域内的构象灵活的肽结合通道，以实现结合特异性。我们还重新确定了DLC 8的猿型溶液结构。DLC 8/靶肽复合物的结构以及蛋白质的动态特性为DLC 8的不同氨基酸序列依赖性靶识别提供了分子基础。(C)北京：科学出版社.
Dyneins are multi-subunit molecular motors that translocate molecular cargoes along microtubules. Other than acting as an essential component of the dynein motor complex, the 89-residue subunit of dynein light chain (DLC8) also regulates a number of other biological events by binding to various proteins and enzymes. Currently known DLC8 targets include neuronal nitric oxide synthase; the proapoptotic Bcl-2 family member protein designated Bim; a Drosophila RNA localization protein Swallow, myosin V, neuronal scaffolding protein GKAP, and I kappaB alpha, an inhibitor of the NF kappaB transcription factor. The DLC8-binding domains of the various targets are confined within a short, continuous stretch of amino acid residues. However, these domains do not share any obvious sequence homology with each other. Here, the three-dimensional structures of DLC8 complexed with two peptides corresponding to the DLC8-binding domains of neuronal nitric oxide synthase and Bim, respectively, were determined by NMR spectroscopy. Although the two DLC8-binding peptides have entirely different amino acid sequences, both peptides bind to the protein with a remarkable similar conformation by engaging the symmetric DLC8 dimer through antiparallel a-sheet augmentation via the beta2 strand of the protein. Structural comparison indicates that the two target peptides use different regions within the conformational flexible peptide-binding channels to achieve binding specificity. We have also redetermined the ape-form solution structure of DLC8 in this work. The structures of the DLC8/target peptide complexes, together with the dynamic properties of the protein, provide a molecular basis of DLC8's diverse amino acid sequence-dependent target recognition. (C) 2001 Academic Press.