title: D316 is critical for the enzymatic activity and HIV-1 restriction potential of human and rhesus APOBEC3B.
abstract: APOBEC3B is one of seven human APOBEC3 DNA cytosine deaminases that function to inhibit the replication and persistence of retroelements and retroviruses. Human APOBEC3B restricts the replication of HIV-1 in HEK293 cells, while our laboratory clone of rhesus macaque APOBEC3B did not. We mapped the restriction determinant to a single amino acid difference that alters enzymatic activity. Human APOBEC3B D316 is catalytically active and capable of restricting HIV-1 while rhesus APOBEC3B N316 is not; swapping these residues alters the activity and restriction phenotypes respectively. Genotyping of primate center rhesus macaques revealed uniform homozygosity for aspartate at position 316. Considering the C-to-T nature of the underlying mutation, we suspect that our rhesus APOBEC3B cDNA was inactivated by its own gene product during subcloning in Escherichia coli. This region has been previously characterized for its role in substrate specificity, but these data indicate it also has a fundamental role in deaminase activity.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, Center for Genome Engineering, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: McDougle
authors.forename: Judd F
authors.initials: JF
authors.lastname: Hultquist
authors.forename: Alex C
authors.initials: AC
authors.lastname: Stabell
authors.forename: Sara L
authors.initials: SL
authors.lastname: Sawyer
authors.forename: Reuben S
authors.initials: RS
authors.lastname: Harris
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005838:Genotype; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D017354:Point Mutation
chemical_list: D003564:Cytidine Deaminase
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