title: Nanostructures of APOBEC3G support a hierarchical assembly model of high molecular mass ribonucleoprotein particles from dimeric subunits.
abstract: Human APOBEC3G (hA3G) is a cytidine deaminase that restricts human immunodeficiency virus (HIV)-1 infection in a vif (the virion infectivity factor from HIV)-dependent manner. hA3G from HIV-permissive activated CD4+ T-cells exists as an inactive, high molecular mass (HMM) complex that can be transformed in vitro into an active, low molecular mass (LMM) variant comparable with that of HIV-non-permissive CD4+ T-cells. Here we present low resolution structures of hA3G in HMM and LMM forms determined by small angle x-ray scattering and advanced shape reconstruction methods. The results show that LMM particles have an extended shape, dissimilar to known cytidine deaminases, featuring novel tail-to-tail dimerization. Shape analysis of LMM and HMM structures revealed how symmetric association of dimers could lead to minimal HMM variants. These observations imply that the disruption of cellular HMM particles may require regulation of protein-RNA, as well as protein-protein interactions, which has implications for therapeutic development.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. joseph_wedekind@urms.rochester.edu
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Wedekind
authors.forename: Richard
authors.initials: R
authors.lastname: Gillilan
authors.forename: Alena
authors.initials: A
authors.lastname: Janda
authors.forename: Jolanta
authors.initials: J
authors.lastname: Krucinska
authors.forename: Jason D
authors.initials: JD
authors.lastname: Salter
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Bennett
authors.forename: Jay
authors.initials: J
authors.lastname: Raina
authors.forename: Harold C
authors.initials: HC
authors.lastname: Smith
mesh_terms: D000071480:APOBEC-3G Deaminase; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D003564:Cytidine Deaminase; D019281:Dimerization; D006801:Humans; D008970:Molecular Weight; D049329:Nanostructures; D009700:Nucleoside Deaminases / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012542:Scattering, Radiation
chemical_list: D012097:Repressor Proteins; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase