The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization
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Authors
Bohn, Markus-FrederikShandilya, Shivender
Silvas, Tania V.
Nalivaika, Ellen A.
Kouno, Takahide
Kelch, Brian A
Ryder, Sean P.
Yilmaz, Nese Kurt
Somasundaran, Mohan
Schiffer, Celia A.
UMass Chan Affiliations
Program in Molecular MedicineDepartment of Pediatrics
Department of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2015-05-05Keywords
BiochemistryMedicinal Chemistry and Pharmaceutics
Medicinal-Pharmaceutical Chemistry
Molecular Biology
Structural Biology
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Show full item recordAbstract
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.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 siteDOI
10.1016/j.str.2015.03.016Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48906PubMed ID
25914058Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.str.2015.03.016