Efimov V P, Morris N R
University of Medicine and Dentistry or New Jersey, Robert Wood Johnson Medical School, Department of Pharmacology, 675 Hoes Lane, Piscataway, New Jersey 08854-5635, USA.
J Cell Biol. 2000 Aug 7;150(3):681-8. doi: 10.1083/jcb.150.3.681.
The nudF gene of the filamentous fungus Aspergillus nidulans acts in the cytoplasmic dynein/dynactin pathway and is required for distribution of nuclei. NUDF protein, the product of the nudF gene, displays 42% sequence identity with the human protein LIS1 required for neuronal migration. Haploinsufficiency of the LIS1 gene causes a malformation of the human brain known as lissencephaly. We screened for multicopy suppressors of a mutation in the nudF gene. The product of the nudE gene isolated in the screen, NUDE, is a homologue of the nuclear distribution protein RO11 of Neurospora crassa. The highly conserved NH(2)-terminal coiled-coil domain of the NUDE protein suffices for protein function when overexpressed. A similar coiled-coil domain is present in several putative human proteins and in the mitotic phosphoprotein 43 (MP43) of X. laevis. NUDF protein interacts with the Aspergillus NUDE coiled-coil in a yeast two-hybrid system, while human LIS1 interacts with the human homologue of the NUDE/RO11 coiled-coil and also the Xenopus MP43 coiled-coil. In addition, NUDF coprecipitates with an epitope-tagged NUDE. The fact that NUDF and LIS1 interact with the same protein domain strengthens the notion that these two proteins are functionally related.
丝状真菌构巢曲霉的nudF基因在细胞质动力蛋白/动力蛋白激活蛋白途径中起作用，是细胞核分布所必需的。nudF基因的产物NUDF蛋白与神经元迁移所需的人类蛋白LIS1具有42%的序列同一性。LIS1基因的单倍剂量不足会导致一种称为无脑回畸形的人类大脑畸形。我们筛选了nudF基因突变的多拷贝抑制子。在筛选中分离出的nudE基因的产物NUDE是粗糙脉孢菌核分布蛋白RO11的同源物。当过度表达时，NUDE蛋白高度保守的NH(2)-末端卷曲螺旋结构域足以发挥蛋白质功能。在几种假定的人类蛋白质和非洲爪蟾的有丝分裂磷蛋白43（MP43）中也存在类似的卷曲螺旋结构域。在酵母双杂交系统中，NUDF蛋白与构巢曲霉的NUDE卷曲螺旋相互作用，而人类LIS1与NUDE/RO11卷曲螺旋的人类同源物以及非洲爪蟾的MP43卷曲螺旋相互作用。此外，NUDF与带有表位标签的NUDE共沉淀。NUDF和LIS1与相同蛋白质结构域相互作用这一事实强化了这两种蛋白质在功能上相关的观点。
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