Complete structure of p97/valosin-containing protein reveals communication between nucleotide domains
Complete structure of p97/valosin-containing protein reveals communication between nucleotide domains
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DOI：
10.1038/nsb972
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发表时间：
2003-10-01
期刊：
影响因子：
--
通讯作者：
Brunger, AT
中科院分区：
文献类型：
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作者：
DeLaBarre, B;Brunger, AT
ATP酶p97/VCP影响细胞内的多个事件。这些事件包括细胞核和有丝分裂高尔基体膜的改变，泛素化蛋白从内质网的移位和NF-κ B通路的调节。在这里，我们提出的晶体结构的全长小家鼠p97/VCP在复杂的ADP和ADP-AlFx的混合物在4.7埃的分辨率。这是第一个完整的六聚体结构的蛋白质含有串联AAA（ATP酶与各种细胞活动）结构域。的晶体结构和冷冻电子显微镜（EM）重建的比较揭示了大的构象变化的螺旋子域在水解周期。结构和功能数据意味着AAA域之间的通信机制。Zn 2+堵塞六聚体的中心孔，表明底物不穿过分子的孔。
The ATPase p97/VCP affects multiple events within the cell. These events include the alteration of both nuclear and mitotic Golgi membranes, the dislocation of ubiquitylated proteins from the endoplasmic reticulum and regulation of the NF-kappab pathway. Here we present the crystal structure of full-length Mus musculus p97/VCP in complex with a mixture of ADP and ADP-AlFx at a resolution of 4.7 Angstrom. This is the first complete hexameric structure of a protein containing tandem AAA ( ATPases associated with a variety of cellular activities) domains. Comparison of the crystal structure and cryo-electron microscopy ( EM) reconstructions reveals large conformational changes in the helical subdomains during the hydrolysis cycle. Structural and functional data imply a communication mechanism between the AAA domains. A Zn2+ occludes the central pore of the hexamer, suggesting that substrate does not thread through the pore of the molecule.