Hexamerization of p97-VCP is promoted by ATP binding to the D1 domain and required for ATPase and biological activities
Hexamerization of p97-VCP is promoted by ATP binding to the D1 domain and required for ATPase and biological activities
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DOI：
10.1016/s0006-291x(02)02840-1
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发表时间：
2003-01-10
影响因子：
3.1
通讯作者：
Li, CCH
中科院分区：
文献类型：
--
作者：
Wang, Q;Song, CC;Li, CCH
含有97 kDa Valosin的蛋白(p97-VCP或VCP)是一种六聚体AAA-ATPase，在包括泛素-蛋白酶体介导的蛋白质降解在内的多种细胞活动中发挥重要作用。在本报告中，我们研究了VCP的解离-重组动力学，以分析VCP的结构与功能的关系。尿素解离的VCP可以自行重组，但加入三磷酸腺苷、二磷酸腺苷或三磷酸腺苷-γ可加速重组。在D1的ATP结合部位的突变，而不是D2，取消了ATP的加速效应，并进一步推迟了重组。利用野生型和ATP结合位点突变体的混合六聚体，我们证明了ATPase活性和泛素-蛋白酶体介导的降解需要六聚体结构和亚基之间的适当沟通。因此，D1中的ATP结合位点在VCP的六聚化过程中起着重要作用，而适当的亚基之间的相互作用对VCP的活性是至关重要的。由爱思唯尔科学(美国)出版。
The 97-kDa valosin-containing protein (p97-VCP or VCP), a hexameric AAA ATPase, plays an important role in diverse cell activities, including ubiquitin-proteasome mediated protein degradation. In this report, we studied dissociation-reassembly kinetics to analyze the structure-function relationship in VCP. Urea-dissociated VCP can reassemble by itself, but addition of ATP, ADP, or ATP-gammaS accelerates the reassembly. Mutation in the ATP-binding site of D1, but not D2, domain abolishes the ATP acceleration effect and further delays the reassembly. Using hybrid hexamers of the wild type and ATP-binding site mutant, we show that hexameric structure and proper communication among the subunits are required for the ATPase activity and ubiquitin-proteasome mediated degradation. Thus, ATP-binding site in D1 plays a major role in VCP hexamerization, of which proper inter-subunit interaction is essential for the activities. Published by Elsevier Science (USA).