6bbo

Crystal structure of human APOBEC3H/RNA complex

spinqualitylabelsall models 6bbo, resolution 3.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bbo is a 8 chain structure with sequence from Dissp, Escherichia coli and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, ZN Related: 6b0b Gene: APOBEC3H (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. The Antiviral and Cancer Genomic DNA Deaminase APOBEC3H Is Regulated by an RNA-Mediated Dimerization Mechanism.,Shaban NM, Shi K, Lauer KV, Carpenter MA, Richards CM, Salamango D, Wang J, Lopresti MW, Banerjee S, Levin-Klein R, Brown WL, Aihara H, Harris RS Mol Cell. 2018 Jan 4;69(1):75-86.e9. doi: 10.1016/j.molcel.2017.12.010. Epub 2017, Dec 28. PMID:29290613 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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