NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity

In-Ja L. Byeon, Jinwoo Ahn, Mithun Mitra, Chang-Hyeock Byeon, Kamil Hercík, Jozef Hritz, Lisa M. Charlton, Judith G. Levin and Angela M. Gronenborn ()
Additional contact information
In-Ja L. Byeon: University of Pittsburgh School of Medicine
Jinwoo Ahn: University of Pittsburgh School of Medicine
Mithun Mitra: Section on Viral Gene Regulation, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Chang-Hyeock Byeon: University of Pittsburgh School of Medicine
Kamil Hercík: Section on Viral Gene Regulation, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Jozef Hritz: University of Pittsburgh School of Medicine
Lisa M. Charlton: University of Pittsburgh School of Medicine
Judith G. Levin: Section on Viral Gene Regulation, Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Angela M. Gronenborn: University of Pittsburgh School of Medicine

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract Human APOBEC3A is a single-stranded DNA cytidine deaminase that restricts viral pathogens and endogenous retrotransposons, and has a role in the innate immune response. Furthermore, its potential to act as a genomic DNA mutator has implications for a role in carcinogenesis. A deeper understanding of APOBEC3A’s deaminase and nucleic acid-binding properties, which is central to its biological activities, has been limited by the lack of structural information. Here we report the nuclear magnetic resonance solution structure of APOBEC3A and show that the critical interface for interaction with single-stranded DNA substrates includes residues extending beyond the catalytic centre. Importantly, by monitoring deaminase activity in real time, we find that A3A displays similar catalytic activity on APOBEC3A-specific TTCA- or A3G-specific CCCA-containing substrates, involving key determinants immediately 5′ of the reactive C. Our results afford novel mechanistic insights into APOBEC3A-mediated deamination and provide the structural basis for further molecular studies.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/ncomms2883 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:4:y:2013:i:1:d:10.1038_ncomms2883

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

DOI: 10.1038/ncomms2883

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 ().