title: Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein.
abstract: The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalysed DNA elongation. Here, we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.
authors.affiliation: Department of Physics, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Kathy R
authors.initials: KR
authors.lastname: Chaurasiya
authors.affiliation: Department of Physics, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Micah J
authors.initials: MJ
authors.lastname: McCauley
authors.affiliation: Department of Chemistry and Biochemistry, Center for Retrovirus Research, and Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, Center for Retrovirus Research, and Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Dominic F
authors.initials: DF
authors.lastname: Qualley
authors.affiliation: Section on Viral Gene Regulation, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Tiyun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi 460-0001, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kitamura
authors.affiliation: Department of Physics, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Hylkje
authors.initials: H
authors.lastname: Geertsema
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Denise S B
authors.initials: DS
authors.lastname: Chan
authors.affiliation: Section on Viral Gene Regulation, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Hertz
authors.affiliation: 1] Section on Viral Gene Regulation, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi 460-0001, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Iwatani
authors.affiliation: Section on Viral Gene Regulation, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Judith G
authors.initials: JG
authors.lastname: Levin
authors.affiliation: Department of Chemistry and Biochemistry, Center for Retrovirus Research, and Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Musier-Forsyth
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Ioulia
authors.initials: I
authors.lastname: Rouzina
authors.affiliation: Department of Physics, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Williams
mesh_terms: D000071480:APOBEC-3G Deaminase; D001704:Biopolymers / Q000737:chemistry*; D003564:Cytidine Deaminase / Q000737:chemistry / Q000378:metabolism*; D003641:Deamination; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014779:Virus Replication
chemical_list: D001704:Biopolymers; D012194:RNA-Directed DNA Polymerase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase