UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Schiffer Lab

Publication Date

2018-06-25

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Enzymes and Coenzymes | Genetic Phenomena | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology | Viruses

Abstract

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.

Rights and Permissions

© The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-018-04872-8

Source

Nat Commun. 2018 Jun 25;9(1):2460. doi: 10.1038/s41467-018-04872-8. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Related Resources

Link to Article in PubMed

PubMed ID

29941968

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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