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PDBsum entry 6b0b
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Hydrolase/RNA
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PDB id
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6b0b
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References listed in PDB file
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Key reference
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Title
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The antiviral and cancer genomic DNA deaminase apobec3h is regulated by an RNA-Mediated dimerization mechanism.
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Authors
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N.M.Shaban,
K.Shi,
K.V.Lauer,
M.A.Carpenter,
C.M.Richards,
D.Salamango,
J.Wang,
M.W.Lopresti,
S.Banerjee,
R.Levin-Klein,
W.L.Brown,
H.Aihara,
R.S.Harris.
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Ref.
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Mol Cell, 2018,
69,
75.
[DOI no: ]
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PubMed id
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Abstract
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Human APOBEC3H and homologous single-stranded DNA cytosine deaminases are unique
to mammals. These DNA-editing enzymes function in innate immunity by restricting
the replication of viruses and transposons. APOBEC3H also contributes to cancer
mutagenesis. Here, we address the fundamental nature of RNA in regulating human
APOBEC3H activities. APOBEC3H co-purifies with RNA as an inactive protein, and
RNase A treatment enables strong DNA deaminase activity. RNA-binding-defective
mutants demonstrate clear separation of function by becoming DNA hypermutators.
Biochemical and crystallographic data demonstrate a mechanism in which
double-stranded RNA mediates enzyme dimerization. Additionally, APOBEC3H
separation-of-function mutants show that RNA binding is required for cytoplasmic
localization, packaging into HIV-1 particles, and antiviral activity. Overall,
these results support a model in which structured RNA negatively regulates the
potentially harmful DNA deamination activity of APOBEC3H while, at the same
time, positively regulating its antiviral activity.
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