title: Cryo-EM structures and atomic model of the HIV-1 strand transfer complex intasome.
abstract: 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.
authors.affiliation: Laboratory of Genetics and Helmsley Center for Genomic Medicine, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Dario Oliveira
authors.initials: DO
authors.lastname: Passos
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Renbin
authors.initials: R
authors.lastname: Yang
authors.affiliation: Center for Retrovirus Research and College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Stephanie V
authors.initials: SV
authors.lastname: Rebensburg
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ghirlando
authors.affiliation: Laboratory of Genetics and Helmsley Center for Genomic Medicine, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Youngmin
authors.initials: Y
authors.lastname: Jeon
authors.affiliation: Center for Retrovirus Research and College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Nikoloz
authors.initials: N
authors.lastname: Shkriabai
authors.affiliation: Center for Retrovirus Research and College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mamuka
authors.initials: M
authors.lastname: Kvaratskhelia
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Craigie
authors.affiliation: Laboratory of Genetics and Helmsley Center for Genomic Medicine, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. dlyumkis@salk.edu.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Lyumkis
mesh_terms: D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D004279:DNA, Viral / Q000737:chemistry / Q000648:ultrastructure; D019427:HIV Integrase / Q000737:chemistry / Q000648:ultrastructure; D015497:HIV-1 / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry / Q000648:ultrastructure; D000072417:Protein Domains; D012367:RNA, Viral / Q000737:chemistry / Q000648:ultrastructure; D016662:Virus Integration
chemical_list: D004279:DNA, Viral; D009698:Nucleoproteins; D012367:RNA, Viral; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1