title: Retroviral integrase protein and intasome nucleoprotein complex structures.
abstract: 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 1980s, 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.
authors.affiliation: Julia Grawenhoff, Alan N Engelman, Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Grawenhoff
authors.affiliation: Julia Grawenhoff, Alan N Engelman, Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, United States.
authors.forename: Alan N
authors.initials: AN
authors.lastname: Engelman
keywords: 3-dimensional structure; DNA integration; Human immunodeficiency virus/acquired immune deficiency syndrome; Intasome; Integrase; Mouse mammary tumor virus; Prototype foamy virus; Retrovirus; Rous sarcoma virus