Retroviral integrase protein and intasome nucleoprotein complex structures

• 作者: Alan N Engelman Julia Grawenhoff
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: DNA 集成 3-dimensional 结构 INTEGRASE Intasome 老鼠乳房的肿瘤病毒 RETROVIRUS Rous 肉瘤病毒 为起泡沫的病毒建原型 人的免疫不全 virus/acquired 免疫者缺乏症候群
• 年，卷（期）: 2017,（1）
• 页码范围: 32-44
• 页数: 13页
• 分类号: R373

摘要

Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct chemical reactions: 3’-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3’-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980 s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus(PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus(RSV) and β-retrovirus mouse mammary tumor virus(MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.