Complementary function of the two catalytic domains of APOBEC3G.
The HIV-1 viral accessory protein Vif prevents the encapsidation of the antiviral cellular cytidine deaminases APOBEC3F and APOBEC3G by inducing their proteasomal degradation. In the absence of Vif, APOBEC3G is encapsidated and blocks virus replication by deaminating cytosines of the viral cDNA. APOBEC3G encapsidation has been recently shown to depend on the viral nucleocapsid protein; however, the role of RNA remains unclear. Using APOBEC3G deletion and point mutants, we mapped the encapsidation determinant to the Zn(2+) coordination residues of the N-terminal catalytic domain (CD1). Notably, these residues were also required for RNA binding. Mutations in the two aromatic residues of CD1 but not CD2, which are conserved in cytidine deaminase core domains and are required for RNA binding, prevented encapsidation into HIV-1, HTLV-I and MLV. The Zn(2+) coordination residues of the C-terminal catalytic domain (CD2) were not required for encapsidation but were essential for cytidine deaminase activity and the antiviral effect. These findings suggest a model in which CD1 mediates encapsidation and RNA binding while CD2 mediates cytidine deaminase activity. Interestingly, HTLV-I was relatively resistant to the antiviral effects of encapsidated APOBEC3G.
Navarro
Francisco
F
Infectious Disease Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bollman
Brooke
B
Chen
Hui
H
König
Renate
R
Yu
Qin
Q
Chiles
Kristopher
K
Landau
Nathaniel R
NR
D000071480:APOBEC-3G Deaminase; D000818:Animals; D001483:Base Sequence; D020134:Catalytic Domain; D003564:Cytidine Deaminase; D004247:DNA / Q000235:genetics; D017353:Gene Deletion; D016346:Gene Products, vif / Q000502:physiology; D005814:Genes, Viral; D016341:Genes, vif; D005816:Genetic Complementation Test; D015658:HIV Infections / Q000201:enzymology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000502:physiology; D051379:Mice; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000502:physiology; D009700:Nucleoside Deaminases; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000502:physiology*; D012097:Repressor Proteins; D019065:Virus Assembly; D014779:Virus Replication / Q000235:genetics / Q000502:physiology; D015032:Zinc / Q000737:chemistry; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D019590:Nucleocapsid Proteins; D011506:Proteins; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D004247:DNA; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; D015032:Zinc