N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors
N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors
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DOI：
10.1242/jcs.111278
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Wang, Jia-huai
中科院分区：
文献类型：
--
作者：
Chen, Qiang;Sun, Xiaqin;Wang, Jia-huai
结肠直肠癌中的神经胶质瘤细胞（DCC）是轴突导向因子netrin-1和draxin的受体。这些引导信号和DCC之间的相互作用在神经系统的发育中起着关键作用。在本研究中，我们揭示了DCC的N-末端四个Ig样结构域的晶体结构。分子折叠成马蹄形结构。我们证明，这种马蹄形构象的DCC所需的指导线索介导的轴突吸引力。破坏DCC马蹄铁的基于结构的突变确实会损害其功能。DCC马蹄形与先前描述的马蹄形结构的比较揭示了惊人的保守的结构特征和重要的序列特征。利用这些特征，全基因组搜索使我们能够预测许多其他细胞表面受体的N-末端马蹄形排列，几乎所有这些受体都在神经系统中发挥作用。N-末端马蹄形似乎是进化选择作为神经受体的平台。
Deleted in colorectal cancer (DCC) is a receptor for the axon guidance cues netrin-1 and draxin. The interactions between these guidance cues and DCC play a key role in the development of the nervous system. In the present study, we reveal the crystal structure of the N-terminal four Ig-like domains of DCC. The molecule folds into a horseshoe-like configuration. We demonstrate that this horseshoe conformation of DCC is required for guidance-cue-mediated axonal attraction. Structure-based mutations that disrupt the DCC horseshoe indeed impair its function. A comparison of the DCC horseshoe with previously described horseshoe structures has revealed striking conserved structural features and important sequence signatures. Using these signatures, a genome-wide search allows us to predict the N-terminal horseshoe arrangement in a number of other cell surface receptors, nearly all of which function in the nervous system. The N-terminal horseshoe appears to be evolutionally selected as a platform for neural receptors.