Model structure of human APOBEC3G

• Published in: PloS one 2007-04, Vol.2 (4), p.e378-e378
• Main Authors: Zhang, Kun-Lin, Mangeat, Bastien, Ortiz, Millan, Zoete, Vincent, Trono, Didier, Telenti, Amalio, Michielin, Olivier
• Format: Article
• Language: English
• Subjects: Amino acids; Antiretroviral agents; APOBEC-3G Deaminase; Apolipoprotein B; Apolipoproteins; Bioinformatics; Blotting, Western; Catalysis; Clusters; Computational Biology/Protein Structure Prediction; Crystal structure; Crystallography, X-Ray; Cytidine Deaminase - chemistry; Cytosine; Cytosine deaminase; Deamination; Deoxyribonucleic acid; DNA; Electrostatic properties; Encapsidation; Enzymes; Functional analysis; HIV; Human immunodeficiency virus; Humans; Infectious Diseases/HIV Infection and AIDS; Infectivity; Life sciences; Magnetic resonance; Microbiology/Innate Immunity; Models, Molecular; mRNA; Mutants; Mutation; NMR; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Packaging; Pathogenesis; Polypeptides; Protein Conformation; Proteins; Pyrimidines; Residues; RNA; RNA editing; Virions
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0000378

APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) has antiretroviral activity associated with the hypermutation of viral DNA through cytosine deamination. APOBEC3G has two cytosine deaminase (CDA) domains; the catalytically inactive amino-terminal domain of APOBEC3G (N-CDA) carries the Vif interaction domain. There is no 3-D structure of APOBEC3G solved by X-ray or nuclear magnetic resonance. We predicted the structure of human APOBEC3G based on the crystal structure of APOBEC2. To assess the model structure, we evaluated 48 mutants of APOBEC3G N-CDA that identify novel variants altering DeltaVif HIV-1 infectivity and packaging of APOBEC3G. Results indicated that the key residue D128 is exposed at the surface of the model, with a negative local electrostatic potential. Mutation D128K changes the sign of that local potential. In addition, two novel functionally relevant residues that result in defective APOBEC3G encapsidation, R122 and W127, cluster at the surface. The structure model identifies a cluster of residues important for packaging of APOBEC3G into virions, and may serve to guide functional analysis of APOBEC3G.