The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization
Silvas, Tania V.
Nalivaika, Ellen A.
Kelch, Brian A
Ryder, Sean P.
Yilmaz, Nese Kurt
Schiffer, Celia A.
UMass Chan AffiliationsProgram in Molecular Medicine
Department of Pediatrics
Department of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
Medicinal Chemistry and Pharmaceutics
MetadataShow full item record
AbstractDeaminase 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.
SourceStructure. 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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/48906
Related ResourcesLink to Article in PubMed