ArticleNature2016
Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 98 citations in OpenAlex.
- Targeting Human Immunodeficiency Virus Integrase Beyond the Active Site: The Discovery and Development of Allosteric Integrase Inhibitors.ChemMedChem · 2026Review
- Core nucleosomes are refractory to lentiviral DNA integration.Nature communications · 2026Article
- Delineation of a novel assembly intermediate in Rous sarcoma virus integration pathway.Nucleic acids research · 2026Article
- Retroviral intasome architecture shapes the dynamics of target DNA search and integration.PLoS pathogens · 2026Article
- Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding.Nature communications · 2025Article
- Integrated Computational Analysis of C-2 Substituted Pyrazolopyrimidine and Amide Isosteres ALLINI: 3D-QSAR, Molecular Docking, and ADMET Studies.Current HIV research · 2025Article
- Article
- HIV-1 Integrase Assembles Multiple Species of Stable Synaptic Complex Intasomes That Are Active for Concerted DNA Integration In vitro.Journal of molecular biology · 2024Article
- Brief Histories of Retroviral Integration Research and Associated International Conferences.Viruses · 2024Review
- Modulation of the functional interfaces between retroviral intasomes and the human nucleosome.mBio · 2023Article
- Unraveling the palindromic and nonpalindromic motifs of retroviral integration site sequences by statistical mixture models.Genome research · 2023Article
- The Integrase: An Overview of a Key Player Enzyme in the Antiviral Scenario.International journal of molecular sciences · 2023Review
- Mechanisms of HIV-1 integrase resistance to dolutegravir and potent inhibition of drug-resistant variants.Science advances · 2023Article
- A proteomic screen of Ty1 integrase partners identifies the protein kinase CK2 as a regulator of Ty1 retrotransposition.Mobile DNA · 2022Article
- Multivalent interactions essential for lentiviral integrase function.Nature communications · 2022Article
- Multimodal Functionalities of HIV-1 Integrase.Viruses · 2022Review
- Structure and function of retroviral integrase.Nature reviews. Microbiology · 2022Review
- Prototype Foamy Virus Integrase Displays Unique Biochemical Activities among Retroviral Integrases.Biomolecules · 2021Article
- Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes.Nature communications · 2021Article
- Ty1 integrase is composed of an active N-terminal domain and a large disordered C-terminal module dispensable for its activity in vitro.The Journal of biological chemistry · 2021Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Retroviral integrase catalyses the integration of viral DNA into host target DNA, which is an essential step in the life cycle of all retroviruses. Previous structural characterization of integrase-viral DNA complexes, or intasomes, from the spumavirus prototype foamy virus revealed a functional integrase tetramer, and it is generally believed that intasomes derived from other retroviral genera use tetrameric integrase. However, the intasomes of orthoretroviruses, which include all known pathogenic species, have not been characterized structurally. Here, using single-particle cryo-electron microscopy and X-ray crystallography, we determine an unexpected octameric integrase architecture for the intasome of the betaretrovirus mouse mammary tumour virus. The structure is composed of two core integrase dimers, which interact with the viral DNA ends and structurally mimic the integrase tetramer of prototype foamy virus, and two flanking integrase dimers that engage the core structure via their integrase carboxy-terminal domains. Contrary to the belief that tetrameric integrase components are sufficient to catalyse integration, the flanking integrase dimers were necessary for mouse mammary tumour virus integrase activity. The integrase octamer solves a conundrum for betaretroviruses as well as alpharetroviruses by providing critical carboxy-terminal domains to the intasome core that cannot be provided in cis because of evolutionarily restrictive catalytic core domain-carboxy-terminal domain linker regions. The octameric architecture of the intasome of mouse mammary tumour virus provides new insight into the structural basis of retroviral DNA integration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.