Title

The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Department of Pediatrics; Program in Molecular Medicine

Publication Date

2015-05-05

Document Type

Article

Disciplines

Biochemistry | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Structural Biology

Abstract

Deaminase activity mediated by the human APOBEC3 family of proteins contributes to genomic instability and cancer. APOBEC3A is by far the most active in this family and can cause rapid cell death when overexpressed, but in general how the activity of APOBEC3s is regulated on a molecular level is unclear. In this study, the biochemical and structural basis of APOBEC3A substrate binding and specificity is elucidated. We find that specific binding of single-stranded DNA is regulated by the cooperative dimerization of APOBEC3A. The crystal structure elucidates this homodimer as a symmetric domain swap of the N-terminal residues. This dimer interface provides insights into how cooperative protein-protein interactions may affect function in the APOBEC3 enzymes and provides a potential scaffold for strategies aimed at reducing their mutation load.

DOI of Published Version

10.1016/j.str.2015.03.016

Source

Structure. 2015 May 5;23(5):903-11. doi: 10.1016/j.str.2015.03.016. Epub 2015 Apr 23. Link to article on publisher's site

Journal/Book/Conference Title

Structure (London, England : 1993)

Related Resources

Link to Article in PubMed

PubMed ID

25914058

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