Structure, interaction and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G

Human APOBEC3G exhibits anti‐human immunodeficiency virus‐1 (HIV‐1) activity by deaminating cytidines of the minus strand of HIV‐1. Here, we report a solution structure of the C‐terminal deaminase domain of wild‐type APOBEC3G. The interaction with DNA was examined. Many differences in the interactio...

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Bibliographic Details
Published in:The EMBO journal 2009-02, Vol.28 (4), p.440-451
Main Authors: Furukawa, Ayako, Nagata, Takashi, Matsugami, Akimasa, Habu, Yuichirou, Sugiyama, Ryuichi, Hayashi, Fumiaki, Kobayashi, Naohiro, Yokoyama, Shigeyuki, Takaku, Hiroshi, Katahira, Masato
Format: Article
Language:English
Subjects:
Animals
APOBEC-3G Deaminase
APOBEC3G
Codon
Cytidine - chemistry
cytidine deaminase
Cytidine Deaminase - chemistry
Cytidine Deaminase - metabolism
Deoxyribonucleic acid
DNA
DNA, Single-Stranded - chemistry
Enzymes
HIV
HIV-1 - metabolism
Human immunodeficiency virus
Humans
Hydrogen-Ion Concentration
Kinetics
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular biology
Molecular Conformation
Mutation
Protein Structure, Tertiary
structure
Vif
vif Gene Products, Human Immunodeficiency Virus - metabolism
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Summary:Human APOBEC3G exhibits anti‐human immunodeficiency virus‐1 (HIV‐1) activity by deaminating cytidines of the minus strand of HIV‐1. Here, we report a solution structure of the C‐terminal deaminase domain of wild‐type APOBEC3G. The interaction with DNA was examined. Many differences in the interaction were found between the wild type and recently studied mutant APOBEC3Gs. The position of the substrate cytidine, together with that of a DNA chain, in the complex, was deduced. Interestingly, the deamination reaction of APOBEC3G was successfully monitored using NMR signals in real time. Real‐time monitoring has revealed that the third cytidine of the d(CCCA) segment is deaminated at an early stage and that then the second one is deaminated at a late stage, the first one not being deaminated at all. This indicates that the deamination is carried out in a strict 3′ → 5′ order. Virus infectivity factor (Vif) of HIV‐1 counteracts the anti‐HIV‐1 activity of APOBEC3G. The structure of the N‐terminal domain of APOBEC3G, with which Vif interacts, was constructed with homology modelling. The structure implies the mechanism of species‐specific sensitivity of APOBEC3G to Vif action.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2008.290