Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Chromatin Structure and Mobile DNA, The Francis Crick Institute, London NW1 1AT, UK; Department of Medicine, Imperial College London, St-Mary's Campus, Norfolk Place, London W2 1PG, UK.
Curr Opin Struct Biol. 2017 Dec;47:23-29. doi: 10.1016/j.sbi.2017.04.005. Epub 2017 Apr 28.
Retroviral DNA integration takes place in the context of the intasome nucleoprotein complex. X-ray crystal structures of functional spumaviral intasomes were previously revealed to harbor a homotetramer of integrase, and it was generally believed that integrase tetramers catalyzed the integration of other retroviruses. The elucidation of new structures from four different retroviruses over the past year has however revealed this is not the case. The number of integrase molecules required to construct the conserved intasome core structure differs between viral species. While four subunits suffice for spumaviruses, α- and β-retroviruses require eight and the lentiviruses use up to sixteen. Herein we described these alternative architectures, highlighting both evolutionary and structural constraints that result in the different integrase-DNA stoichiometries across Retroviridae.
逆转录病毒 DNA 的整合发生在整合体核蛋白复合物的环境中。以前的 X 射线晶体结构揭示了功能性泡沫病毒整合体含有整合酶的同源四聚体，并且普遍认为整合酶四聚体催化了其他逆转录病毒的整合。然而，在过去的一年中，从四种不同的逆转录病毒中阐明的新结构表明情况并非如此。构建保守的整合体核心结构所需的整合酶分子数量因病毒种类而异。虽然四个亚基足以满足泡沫病毒的需要，但α-和β-逆转录病毒需要八个，而慢病毒则需要多达十六个。在此，我们描述了这些替代结构，强调了导致逆转录病毒科中不同整合酶-DNA 计量比的进化和结构限制。
