Cryo-EM structures and atomic model of the HIV-1 strand transfer complex intasome

Like all retroviruses, HIV-1 irreversibly inserts a viral DNA (vDNA) copy of its RNA genome into host target DNA (tDNA). The intasome, a higher-order nucleoprotein complex composed of viral integrase (IN) and the ends of linear vDNA, mediates integration. Productive integration into host chromatin r...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2017-01, Vol.355 (6320), p.89-92
Main Authors: Passos, Dario Oliveira, Li, Min, Yang, Renbin, Rebensburg, Stephanie V., Ghirlando, Rodolfo, Jeon, Youngmin, Shkriabai, Nikoloz, Kvaratskhelia, Mamuka, Craigie, Robert, Lyumkis, Dmitry
Format: Article
Language:English
Subjects:
Assembly
Atomic structure
Cryoelectron Microscopy
Crystallography, X-Ray
Deoxyribonucleic acid
DNA
DNA, Viral - chemistry
DNA, Viral - ultrastructure
Electron microscopy
Enzymes
Genomes
High resolution
HIV
HIV Integrase - chemistry
HIV Integrase - ultrastructure
HIV-1 - chemistry
HIV-1 - physiology
HIV-1 - ultrastructure
Human immunodeficiency virus
Humans
Infections
Inserts
Lentivirus
Life cycle engineering
Maedi-visna virus
Models, Molecular
Modules
Nucleoproteins - chemistry
Nucleoproteins - ultrastructure
Protein Domains
Retroviridae
Ribonucleic acid
RNA
RNA, Viral - chemistry
RNA, Viral - ultrastructure
Strands
Transmission electron microscopy
Virus Integration
Viruses
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Description
Summary:Like all retroviruses, HIV-1 irreversibly inserts a viral DNA (vDNA) copy of its RNA genome into host target DNA (tDNA). The intasome, a higher-order nucleoprotein complex composed of viral integrase (IN) and the ends of linear vDNA, mediates integration. Productive integration into host chromatin results in the formation of the strand transfer complex (STC) containing catalytically joined vDNA and tDNA. HIV-1 intasomes have been refractory to high-resolution structural studies. We used a soluble IN fusion protein to facilitate structural studies, through which we present a high-resolution cryo–electron microscopy (cryo-EM) structure of the core tetrameric HIV-1 STC and a higher-order form that adopts carboxyl-terminal domain rearrangements. The distinct STC structures highlight how HIV-1 can use the common retroviral intasome core architecture to accommodate different IN domain modules for assembly.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aah5163