The prion protein has DNA strand transfer properties similar to retroviral nucleocapsid protein
The prion protein has DNA strand transfer properties similar to retroviral nucleocapsid protein
复制标题
DOI：
10.1006/jmbi.2001.4544
复制
发表时间：
2001-04-06
影响因子：
5.6
通讯作者：
Darlix, JL
中科院分区：
文献类型：
--
作者：
Gabus, C;Auxilien, S;Darlix, JL
传染性海绵状脑病是一种致命的神经退行性疾病，与细胞内抗蛋白酶型蛋白(PrP)的积聚有关。虽然PrP在脊椎动物中高度保守并广泛表达，但它的功能仍然是一个推测的问题。事实上，PrP基因缺失的小鼠发育正常，是健康的。最近的研究结果表明，PrP在体外与核酸结合，并被发现与逆转录病毒颗粒有关。此外，在小鼠身上，MuLV的复制似乎加速了瘙痒病的感染过程。这些观察结果促使我们进一步研究PrP与核酸的相互作用，并将其与逆转录病毒核衣壳蛋白(NC)的相互作用进行比较。NC蛋白作为逆转录病毒颗粒的主要核酸结合蛋白，与病毒核衣壳中的基因组RNA紧密结合，通过逆转录酶陪伴前病毒DNA的合成。我们的结果表明，人类PrP蛋白(HuPrP)在功能上与HIV-1的NCp7相似。这两种蛋白质在与DNA结合后形成大的核蛋白复合体。在产生长末端重复序列所必需的正负DNA链转导过程中，它们加速互补DNA链的杂交和伴侣病毒DNA的合成。HuPrP的DNA结合和链转移特性似乎映射到由23到144个残基组成的N-末端片段，而C-末端结构域是不活跃的。这些发现提示PrP可能参与体内的核酸代谢。(C)2001年学术出版社。
The transmissible spongiform encephalopathies are fatal neurodegenerative diseases that are associated with the accumulation of a protease-resistant form of the cellular prion protein (PrP). Although PrP is highly conserved and widely expressed in vertebrates, its function remains a matter of speculation. Indeed PrP null mice develop normally and are healthy. Recent results show that PrP binds to nucleic acids in vitro and is found associated with retroviral particles. Furthermore, in mice the scrapie infectious process appears to be accelerated by MuLV replication. These observations prompted us to further investigate the interaction between PrP and nucleic acids, and compare it with that of the retroviral nucleocapsid protein (NC). As the major nucleic acid-binding protein of the retroviral particle, NC protein is tightly associated with the genomic RNA in the virion nucleocapsid, where it chaperones proviral DNA synthesis by reverse transcriptase. Our results show that the human prion protein (huPrP) functionally resembles NCp7 of HIV-1. Both proteins form large nucleoprotein complexes upon binding to DNA. They accelerate the hybridization of complementary DNA strands and chaperone viral DNA synthesis during the minus and plus DNA strand tranfers necessary to generate the long terminal repeats. The DNA-binding and strand transfer properties of huPrP appear to map to the N-terminal fragment comprising residues 23 to 144, whereas the C-terminal domain is inactive. These findings suggest that PrP could be involved in nucleic acid metabolism in vivo. (C) 2001 Academic Press.