Extensive mutagenesis experiments corroborate a structural model for the DNA deaminase domain of APOBEC3G

Edited by Hans Eklund

Received 10 July 2007; received in revised form 29 August 2007; accepted 30 August 2007. published online 07 September 2007.

Abstract

APOBEC3G is a single-strand DNA cytosine deaminase capable of blocking retrovirus and retrotransposon replication. APOBEC3G has two conserved zinc-coordinating motifs but only one is required for catalysis. Here, deletion analyses revealed that the minimal catalytic domain consists of residues 198-384. Size exclusion assays indicated that this protein is monomeric. Many (31/69) alanine substitution derivatives of APOBEC3G198-384 retained significant to full levels of activity. These data corroborated an APOBEC2-based structural model for the catalytic domain of APOBEC3G indicating that most non-essential residues are solvent accessible and most essential residues cluster within the protein core.

Abbreviation: APOBEC3G, apolipoprotein BmRNA editing catalytic subunit-like protein 3G

Keywords: APOBEC3G, DNA cytosine deamination, DNA editing, Hypermutation

a University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis, MN 55455, United States

b University of Minnesota, Institute for Molecular Virology, Minneapolis, MN 55455, United States

c University of Minnesota, Beckman Center for Transposon Research, Minneapolis, MN 55455, United States

Corresponding authors. Address: University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis, MN 55455, United States. Fax: +1 612 625 2163.

1 Equal contributions.

PII: S0014-5793(07)00963-5

doi:10.1016/j.febslet.2007.08.076

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