4XXO

Crystal Structure of Human APOBEC3A

Summary for 4XXO

• Entry DOI: 10.2210/pdb4xxo/pdb
• Descriptor: DNA dC->dU-editing enzyme APOBEC-3A, ZINC ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: apobec, apobec3, deaminase, deamination, apolipoprotein b mrna editing polypeptide-like 3, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 47129.33

Authors

Bohn, M.F.,Shandilya, S.M.D.,Schiffer, C.A. (deposition date: 2015-01-30, release date: 2015-04-29, Last modification date: 2024-11-06)

Primary citation

Bohn, M.F.,Shandilya, S.M.,Silvas, T.V.,Nalivaika, E.A.,Kouno, T.,Kelch, B.A.,Ryder, S.P.,Kurt-Yilmaz, N.,Somasundaran, M.,Schiffer, C.A.
The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization.
Structure, 23:903-911, 2015

PubMed 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.

PubMed: 25914058
DOI: 10.1016/j.str.2015.03.016

Experimental method

X-RAY DIFFRACTION (2.843 Å)