Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA

Nat Commun. 2018 Jun 25;9(1):2460. doi: 10.1038/s41467-018-04872-8.


The human APOBEC3G protein is a cytidine deaminase that generates cytidine to deoxy-uridine mutations in single-stranded DNA (ssDNA), and capable of restricting replication of HIV-1 by generating mutations in viral genome. The mechanism by which APOBEC3G specifically deaminates 5'-CC motifs has remained elusive since structural studies have been hampered due to apparently weak ssDNA binding of the catalytic domain of APOBEC3G. We overcame the problem by generating a highly active variant with higher ssDNA affinity. Here, we present the crystal structure of this variant complexed with a ssDNA substrate at 1.86 Å resolution. This structure reveals atomic-level interactions by which APOBEC3G recognizes a functionally-relevant 5'-TCCCA sequence. This complex also reveals a key role of W211 in substrate recognition, implicating a similar recognition in activation-induced cytidine deaminase (AID) with a conserved tryptophan.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • APOBEC-3G Deaminase / chemistry*
  • Catalytic Domain / physiology*
  • Cell Line
  • Crystallography, X-Ray
  • Cytidine / chemistry
  • DNA, Single-Stranded / chemistry*
  • HEK293 Cells
  • HIV-1 / genetics
  • Humans
  • Models, Molecular
  • Protein Structure, Secondary
  • Virus Replication / genetics


  • DNA, Single-Stranded
  • Cytidine
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human