View source for 6bwy


==DNA substrate selection by APOBEC3G==
<StructureSection load='6bwy' size='340' side='right'caption='[[6bwy]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6bwy]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BWY 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <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=6bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bwy OCA], [https://pdbe.org/6bwy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bwy RCSB], [https://www.ebi.ac.uk/pdbsum/6bwy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bwy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POT1_SCHPO POT1_SCHPO] Single-stranded telomeric DNA-binding protein that is required to protect the 3'-end telomeric overhang. It binds the consensus sequence 5'-GGTTAC-3'. Regulates telomerase and telomere length.<ref>PMID:11349150</ref> <ref>PMID:12463756</ref> <ref>PMID:18535244</ref> [https://www.uniprot.org/uniprot/ABC3G_HUMAN ABC3G_HUMAN] DNA deaminase (cytidine deaminase) that mediates a form of innate resistance to retroviral infections (at least to HIV-1 infection) by triggering G-to-A hypermutation in the newly synthesized viral DNA. The replacements C-to-U in the minus strand DNA of HIV-1 during reverse transcription, leads to G-to-A transitions in the plus strand. The inhibition of viral replication is either due to the degradation of the minus strand before its integration or to the lethality of the hypermutations. Modification of both DNA strands is not excluded. This antiviral activity is neutralized by the virion infectivity factor (VIF), that prevents the incorporation of APOBEC3G into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome. May also prevent the transposition of a subset of retroelements. Binds a variety of RNAs, but does not display detectable APOB, NF1 and NAT1 mRNA editing.<ref>PMID:14557625</ref> <ref>PMID:12167863</ref> <ref>PMID:12808466</ref> <ref>PMID:12809610</ref> <ref>PMID:12808465</ref> <ref>PMID:12859895</ref> <ref>PMID:12970355</ref> <ref>PMID:14528300</ref> <ref>PMID:15031497</ref> <ref>PMID:16527742</ref> <ref>PMID:21123384</ref> <ref>PMID:18288108</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (A3) proteins are a family of cytidine deaminases that catalyze the conversion of deoxycytidine (dC) to deoxyuridine (dU) in single-stranded DNA (ssDNA). A3 proteins act in the innate immune response to viral infection by mutating the viral ssDNA. One of the most well-studied human A3 family members is A3G, which is a potent inhibitor of HIV-1. Each A3 protein prefers a specific substrate sequence for catalysis-for example, A3G deaminates the third dC in the CCCA sequence motif. However, the interaction between A3G and ssDNA is difficult to characterize due to poor solution behavior of the full-length protein and loss of DNA affinity of the truncated protein. Here, we present a novel DNA-anchoring fusion strategy using the protection of telomeres protein 1 (Pot1) which has nanomolar affinity for ssDNA, with which we captured an A3G-ssDNA interaction. We crystallized a non-preferred adenine in the -1 nucleotide-binding pocket of A3G. The structure reveals a unique conformation of the catalytic site loops that sheds light onto how the enzyme scans substrate in the -1 pocket. Furthermore, our biochemistry and virology studies provide evidence that the nucleotide-binding pockets on A3G influence each other in selecting the preferred DNA substrate. Together, the results provide insights into the mechanism by which A3G selects and deaminates its preferred substrates and help define how A3 proteins are tailored to recognize specific DNA sequences. This knowledge contributes to a better understanding of the mechanism of DNA substrate selection by A3G, as well as A3G antiviral activity against HIV-1.

Insights into DNA substrate selection by APOBEC3G from structural, biochemical, and functional studies.,Ziegler SJ, Liu C, Landau M, Buzovetsky O, Desimmie BA, Zhao Q, Sasaki T, Burdick RC, Pathak VK, Anderson KS, Xiong Y PLoS One. 2018 Mar 29;13(3):e0195048. doi: 10.1371/journal.pone.0195048., eCollection 2018. PMID:29596531<ref>PMID:29596531</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6bwy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Schizosaccharomyces pombe 972h-]]
[[Category: Synthetic construct]]
[[Category: Buzovetsky O]]
[[Category: Ziegler SJ]]