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dc.contributor.authorBohn, Markus-Frederik
dc.contributor.authorShandilya, Shivender
dc.contributor.authorSilvas, Tania V.
dc.contributor.authorNalivaika, Ellen A.
dc.contributor.authorKouno, Takahide
dc.contributor.authorKelch, Brian A
dc.contributor.authorRyder, Sean P.
dc.contributor.authorYilmaz, Nese Kurt
dc.contributor.authorSomasundaran, Mohan
dc.contributor.authorSchiffer, Celia A.
dc.date2022-08-11T08:10:52.000
dc.date.accessioned2022-08-23T17:23:12Z
dc.date.available2022-08-23T17:23:12Z
dc.date.issued2015-05-05
dc.date.submitted2016-01-25
dc.identifier.citationStructure. 2015 May 5;23(5):903-11. doi: 10.1016/j.str.2015.03.016. Epub 2015 Apr 23. <a href="http://dx.doi.org/10.1016/j.str.2015.03.016">Link to article on publisher's site</a>
dc.identifier.issn0969-2126 (Linking)
dc.identifier.doi10.1016/j.str.2015.03.016
dc.identifier.pmid25914058
dc.identifier.urihttp://hdl.handle.net/20.500.14038/48906
dc.description.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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25914058&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.str.2015.03.016
dc.subjectBiochemistry
dc.subjectMedicinal Chemistry and Pharmaceutics
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.subjectMolecular Biology
dc.subjectStructural Biology
dc.titleThe ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization
dc.typeJournal Article
dc.source.journaltitleStructure (London, England : 1993)
dc.source.volume23
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/schiffer/9
dc.identifier.contextkey8044971
html.description.abstract<p>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.</p>
dc.identifier.submissionpathschiffer/9
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Pediatrics
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages903-11


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