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The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization.
- Source :
-
Structure (London, England : 1993) [Structure] 2015 May 05; Vol. 23 (5), pp. 903-911. Date of Electronic Publication: 2015 Apr 23. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Binding Sites
Crystallography, X-Ray
Cytidine Deaminase genetics
Dimerization
Humans
Models, Molecular
Mutation
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins genetics
Substrate Specificity
Zinc metabolism
Cytidine Deaminase chemistry
Cytidine Deaminase metabolism
DNA, Single-Stranded metabolism
Proteins chemistry
Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-4186
- Volume :
- 23
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Structure (London, England : 1993)
- Publication Type :
- Academic Journal
- Accession number :
- 25914058
- Full Text :
- https://doi.org/10.1016/j.str.2015.03.016