Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity

Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender M. D. Shandilya, Markus F. Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo and Celia A. Schiffer ()
Additional contact information
Takahide Kouno: University of Massachusetts Medical School
Tania V. Silvas: University of Massachusetts Medical School
Brendan J. Hilbert: University of Massachusetts Medical School
Shivender M. D. Shandilya: University of Massachusetts Medical School
Markus F. Bohn: University of Massachusetts Medical School
Brian A. Kelch: University of Massachusetts Medical School
William E. Royer: University of Massachusetts Medical School
Mohan Somasundaran: Program in Molecular Medicine, University of Massachusetts Medical School
Nese Kurt Yilmaz: University of Massachusetts Medical School
Hiroshi Matsuo: Basic Research Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory
Celia A. Schiffer: University of Massachusetts Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 Å. This structure not only visualizes the active site poised for catalysis of APOBEC3A, but pinpoints the residues that confer specificity towards CC/TC motifs. The APOBEC3A–ssDNA complex defines the 5′–3′ directionality and subtle conformational changes that clench the ssDNA within the binding groove, revealing the architecture and mechanism of ssDNA recognition that is likely conserved among all polynucleotide deaminases, thereby opening the door for the design of mechanistic-based therapeutics.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/ncomms15024 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15024

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15024

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().