title: Single-Molecule Force Spectroscopy Studies of APOBEC3A-Single-Stranded DNA Complexes.
abstract: APOBEC3A (A3A) inhibits the replication of a range of viruses and transposons and might also play a role in carcinogenesis. It is a single-domain deaminase enzyme that interacts with single-stranded DNA (ssDNA) and converts cytidines to uridines within specific trinucleotide contexts. Although there is abundant information that describes the potential biological activities of A3A, the interplay between binding ssDNA and sequence-specific deaminase activity remains controversial. Using a single-molecule atomic force microscopy spectroscopy approach developed by Shlyakhtenko et al. [(2015) Sci. Rep. 5, 15648], we determine the stability of A3A in complex with different ssDNA sequences. We found that the strength of the complex is sequence-dependent, with more stable complexes formed with deaminase-specific sequences. A correlation between the deaminase activity of A3A and the complex strength was identified. The ssDNA binding properties of A3A and those for A3G are also compared and discussed.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center , Omaha, Nebraska 68198-6000, United States.
authors.forename: Luda S
authors.initials: LS
authors.lastname: Shlyakhtenko
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center , Omaha, Nebraska 68198-6000, United States.
authors.forename: Samrat
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Center for Genome Engineering, Masonic Cancer Center, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, Institute for Molecular Virology, Center for Genome Engineering, Masonic Cancer Center, University of Minnesota , Minneapolis, Minnesota 55455, United States.|Howard Hughes Medical Institute, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Reuben S
authors.initials: RS
authors.lastname: Harris
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center , Omaha, Nebraska 68198-6000, United States.
authors.forename: Yuri L
authors.initials: YL
authors.lastname: Lyubchenko
mesh_terms: D003564:Cytidine Deaminase / Q000737:chemistry* / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000378:metabolism*; D003641:Deamination; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D011506:Proteins; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase