6b0b: Difference between revisions
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The | ==Crystal structure of human APOBEC3H== | ||
<StructureSection load='6b0b' size='340' side='right'caption='[[6b0b]], [[Resolution|resolution]] 3.28Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6b0b]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Discosoma_sp. Discosoma sp.], [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B0B FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2800622Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6b0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b0b OCA], [https://pdbe.org/6b0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b0b RCSB], [https://www.ebi.ac.uk/pdbsum/6b0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b0b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ABC3H_HUMAN ABC3H_HUMAN] DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms (PubMed:16571802, PubMed:16920826, PubMed:18779051, PubMed:18827027, PubMed:20062055, PubMed:22915799, PubMed:29290613). The A3H-var/haplotype 2 exhibits antiviral activity against vif-deficient HIV-1 (PubMed:18299330, PubMed:21835787, PubMed:23097438, PubMed:29290613). After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA (PubMed:18299330). The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells (PubMed:18299330). Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA (PubMed:20062055). Exhibits antiviral activity also against T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons (PubMed:20062055, PubMed:22457529).<ref>PMID:16571802</ref> <ref>PMID:16920826</ref> <ref>PMID:18299330</ref> <ref>PMID:18779051</ref> <ref>PMID:18827027</ref> <ref>PMID:20062055</ref> <ref>PMID:21835787</ref> <ref>PMID:22457529</ref> <ref>PMID:22915799</ref> <ref>PMID:23097438</ref> <ref>PMID:29290613</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:29290613</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6b0b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Green Fluorescent Protein 3D structures|Green Fluorescent Protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Discosoma sp]] | |||
[[Category: Escherichia coli]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Aihara H]] | |||
[[Category: Banerjee S]] | |||
[[Category: Harris RS]] | |||
[[Category: Shaban NM]] | |||
[[Category: Shi K]] | |||