Structural basis for packaging the dimeric genome of Moloney murine leukaemia virus
- 30 September 2004
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 431 (7008), 586-590
- https://doi.org/10.1038/nature02944
Abstract
All retroviruses specifically package two copies of their genomes during virus assembly, a requirement for strand-transfer-mediated recombination during reverse transcription1,2. Genomic RNA exists in virions as dimers, and the overlap of RNA elements that promote dimerization and encapsidation suggests that these processes may be coupled3,4,5. Both processes are mediated by the nucleocapsid domain (NC) of the retroviral Gag polyprotein3. Here we show that dimerization-induced register shifts in base pairing within the Ψ-RNA packaging signal of Moloney murine leukaemia virus (MoMuLV) expose conserved UCUG elements that bind NC with high affinity (dissociation constant = 75 ± 12 nM). These elements are base-paired and do not bind NC in the monomeric RNA. The structure of the NC complex with a 101-nucleotide ‘core encapsidation’ segment of the MoMuLV Ψ site6 reveals a network of interactions that promote sequence- and structure-specific binding by NC's single CCHC zinc knuckle. Our findings support a structural RNA switch mechanism for genome encapsidation, in which protein binding sites are sequestered by base pairing in the monomeric RNA and become exposed upon dimerization to promote packaging of a diploid genome.This publication has 20 references indexed in Scilit:
- Dimerization of retroviral RNA genomes: an inseparable pairNature Reviews Microbiology, 2004
- Bipartite Signal for Genomic RNA Dimerization in Moloney Murine Leukemia VirusJournal of Virology, 2002
- Two alternating structures of the HIV-1 leader RNARNA, 2001
- A retroviral RNA kissing complex containing only two G⋅C base pairsProceedings of the National Academy of Sciences of the United States of America, 2000
- An additional dimer linkage structure in moloney murine leukemia virus RNAJournal of Molecular Biology, 1999
- RNA PackagingCurrent Topics in Microbiology and Immunology, 1996
- Effect of dimerization on the conformation of the encapsidation Psi domain of Moloney murine leukemia virus RNAJournal of Molecular Biology, 1992
- Retroviral Recombination and Reverse TranscriptionScience, 1990
- Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirusCell, 1983
- Form and Function of Retroviral ProvirusesScience, 1982