Structural requirements for association of neurofascin with ankyrin
Structural requirements for association of neurofascin with ankyrin
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DOI：
10.1074/jbc.273.46.30785
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发表时间：
1998-11-13
影响因子：
4.8
通讯作者：
Bennett, V
中科院分区：
文献类型：
--
作者：
Zhang, X;Davis, JQ;Bennett, V
本文首次对细胞黏附分子L1CAM家族中高度保守的神经束蛋白胞质结构域进行了结构分析，并描述了活细胞中神经束蛋白-锚蛋白相互作用的序列要求。神经束蛋白的胞质结构域在溶液中二聚，具有不对称的形状，并呈现可逆的温度依赖的β结构。残基Ser(56)-Tyr(81)是锚定蛋白结合所必需的，但不有助于二聚化或结构的形成。转GFP基因的神经束蛋白将270-kDa的锚蛋白募集到人胚胎肾293细胞的细胞膜上。缺失突变表明，序列Ser(56)-Tyr(81)含有神经束蛋白的主要强韧蛋白募集活性，FIGQY酪氨酸(Y81H/A/E)突变极大地削弱了神经束蛋白-锚蛋白的相互作用。人类L1等同酪氨酸(Y1229H)突变是导致某些智力低下的原因(Van Camp，G，，Fransen，E.，Vits，L，Raes，G，和Willems，P，J，(1996)Hum。穆塔特。8,391)。突变F77A和E73Q极大地削弱了锚蛋白结合活性，而突变D74N和D57N/D58N/D62N的三个突变导致锚蛋白结合活性损失较少。这些结果为锚蛋白和神经筋膜蛋白之间的高度特异性相互作用提供了证据，并表明锚蛋白与L1之间的联系是人类L1功能所必需的。
This paper presents the first structural analysis of the cytoplasmic domain of neurofascin, which is highly conserved among the L1CAM family of cell adhesion molecules, and describes sequence requirements for neurofascin-ankyrin interactions in living cells. The cytoplasmic domain of neurofascin dimerizes in solution, has an asymmetric shape, and exhibits a reversible temperature-dependent beta-structure. Residues Ser(56)-Tyr(81) are necessary for ankyrin binding but do not contribute to either dimerization or formation of structure. Transfected neurofascin recruits GFP-tagged 270-kDa ankyrin, to the plasma membrane of human embryo kidney 293 cells. Deletion mutants demonstrate that the sequence Ser(56)-Tyr(81) contains the major ankyrin-recruiting activity of neurofascin, Mutations of the FIGQY tyrosine (Y81H/A/E) greatly impair neurofascin-ankyrin interactions. Mutation of human L1 at the equivalent tyrosine (Y1229H) is responsible for certain cases of mental retardation (Van Camp, G,, Fransen, E., Vits, L,, Raes, G,, and Willems, P, J, (1996) Hum. Mutat. 8, 391). Mutations F77A and E73Q greatly impair ankyrin binding activity, whereas mutation D74N and a triple mutation of D57N/D58N/D62N result in less loss of ankyrin binding activity. These results provide evidence for a highly specific interaction between ankyrin and neurofascin and suggest that ankyrin association with L1 is required for L1 function in humans.