Oligomerization Transforms Human APOBEC3G from an Efficient Enzyme to a Slowly Dissociating Nucleic Acid-binding Protein

Overview

Journal Nat Chem

Specialty Chemistry

Date 2013 Dec 19

PMID 24345943

Citations 48

Authors

Kathy R Chaurasiya

Micah J McCauley

Wei Wang

Dominic F Qualley

Tiyun Wu

Shingo Kitamura

Hylkje Geertsema

Denise S B Chan

Amber Hertz

Yasumasa Iwatani

Judith G Levin

Karin Musier-Forsyth

Ioulia Rouzina

Mark C Williams

Affiliations

Soon will be listed here.

Abstract

The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalysed DNA elongation. Here, we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.

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