Department of Biochemistry and Molecular Pharmacology; Schiffer Lab
Amino Acids, Peptides, and Proteins | Enzymes and Coenzymes | Genetic Phenomena | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology | Viruses
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 A 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.
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DOI of Published Version
Nat Commun. 2018 Jun 25;9(1):2460. doi: 10.1038/s41467-018-04872-8. Link to article on publisher's site
Maiti, Atanu; Myint, Wazo; Kanai, Tapan; Delviks-Frankenberry, Krista; Sierra Rodriguez, Christina; Pathak, Vinay K.; Schiffer, Celia A.; and Matsuo, Hiroshi, "Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA" (2018). Open Access Articles. 3523.
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This work is licensed under a Creative Commons Attribution 4.0 License.