5w45

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of APOBEC3H

Structural highlights

5w45 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.486Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11]

Publication Abstract from PubMed

APOBEC3H (A3H) is a member of the APOBEC3 subfamily of DNA cytosine deaminases that are important for innate immune defense and have been implicated in cancer biogenesis. To understand the structural basis for A3H biochemical function, we determined a high-resolution structure of human A3H and performed extensive biochemical analysis. The 2.49 A crystal structure reveals a uniquely long C-terminal helix 6 (h6), a disrupted beta5 strand of the canonical five-stranded beta-sheet core, and a long loop 1 around the Zn-active center. Mutation of a loop 7 residue, W115, disrupted the RNA-mediated dimerization of A3H yielding an RNA-free monomeric form that still possessed nucleic acid binding and deaminase activity. A3H expressed in HEK293T cells showed RNA dependent HMW complex formation and RNase A-dependent deaminase activity. A3H has a highly positively charged surface surrounding the Zn-active center, and multiple positively charged residues within this charged surface play an important role in the RNA-mediated HMW formation and deaminase inhibition. Furthermore, these positively charged residues affect subcellular localization of A3H between the nucleus and cytosol. Finally, we have identified multiple residues of loop 1 and 7 that contribute to the overall deaminase activity and the methylcytosine selectivity.

Understanding the Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H.,Ito F, Yang H, Xiao X, Li SX, Wolfe A, Zirkle B, Arutiunian V, Chen XS Sci Rep. 2018 Feb 28;8(1):3763. doi: 10.1038/s41598-018-21955-0. PMID:29491387^[12]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ OhAinle M, Kerns JA, Malik HS, Emerman M. Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H. J Virol. 2006 Apr;80(8):3853-62. PMID:16571802 doi:10.1128/JVI.80.8.3853-3862.2006
↑ Dang Y, Wang X, Esselman WJ, Zheng YH. Identification of APOBEC3DE as another antiretroviral factor from the human APOBEC family. J Virol. 2006 Nov;80(21):10522-33. PMID:16920826 doi:10.1128/JVI.01123-06
↑ Dang Y, Siew LM, Wang X, Han Y, Lampen R, Zheng YH. Human cytidine deaminase APOBEC3H restricts HIV-1 replication. J Biol Chem. 2008 Apr 25;283(17):11606-14. PMID:18299330 doi:10.1074/jbc.M707586200
↑ OhAinle M, Kerns JA, Li MM, Malik HS, Emerman M. Antiretroelement activity of APOBEC3H was lost twice in recent human evolution. Cell Host Microbe. 2008 Sep 11;4(3):249-59. PMID:18779051 doi:10.1016/j.chom.2008.07.005
↑ Tan L, Sarkis PT, Wang T, Tian C, Yu XF. Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity against retrotransposons and HIV-1. FASEB J. 2009 Jan;23(1):279-87. PMID:18827027 doi:10.1096/fj.07-088781
↑ Stenglein MD, Burns MB, Li M, Lengyel J, Harris RS. APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nat Struct Mol Biol. 2010 Feb;17(2):222-9. doi: 10.1038/nsmb.1744. Epub 2010 Jan , 10. PMID:20062055 doi:10.1038/nsmb.1744
↑ Hultquist JF, Lengyel JA, Refsland EW, LaRue RS, Lackey L, Brown WL, Harris RS. Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1. J Virol. 2011 Nov;85(21):11220-34. doi: 10.1128/JVI.05238-11. Epub 2011 Aug 10. PMID:21835787 doi:10.1128/JVI.05238-11
↑ Ooms M, Krikoni A, Kress AK, Simon V, Munk C. APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-lymphotropic virus type 1. J Virol. 2012 Jun;86(11):6097-108. doi: 10.1128/JVI.06570-11. Epub 2012 Mar 28. PMID:22457529 doi:10.1128/JVI.06570-11
↑ Phalora PK, Sherer NM, Wolinsky SM, Swanson CM, Malim MH. HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies. J Virol. 2012 Nov;86(21):11712-24. doi: 10.1128/JVI.00595-12. Epub 2012 Aug 22. PMID:22915799 doi:10.1128/JVI.00595-12
↑ Chaipan C, Smith JL, Hu WS, Pathak VK. APOBEC3G restricts HIV-1 to a greater extent than APOBEC3F and APOBEC3DE in human primary CD4+ T cells and macrophages. J Virol. 2013 Jan;87(1):444-53. doi: 10.1128/JVI.00676-12. Epub 2012 Oct 24. PMID:23097438 doi:10.1128/JVI.00676-12
↑ 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. The Antiviral and Cancer Genomic DNA Deaminase APOBEC3H Is Regulated by an RNA-Mediated Dimerization Mechanism. Mol Cell. 2018 Jan 4;69(1):75-86.e9. doi: 10.1016/j.molcel.2017.12.010. Epub 2017, Dec 28. PMID:29290613 doi:http://dx.doi.org/10.1016/j.molcel.2017.12.010
↑ Ito F, Yang H, Xiao X, Li SX, Wolfe A, Zirkle B, Arutiunian V, Chen XS. Understanding the Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H. Sci Rep. 2018 Feb 28;8(1):3763. doi: 10.1038/s41598-018-21955-0. PMID:29491387 doi:http://dx.doi.org/10.1038/s41598-018-21955-0

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5w45"

@@ Line 1: / Line 1: @@
 ==Crystal structure of APOBEC3H==
-<StructureSection load='5w45' size='340' side='right' caption='[[5w45]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
+<StructureSection load='5w45' size='340' side='right'caption='[[5w45]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5w45]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W45 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W45 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5w45]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W45 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W45 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.486&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5w45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w45 OCA], [http://pdbe.org/5w45 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w45 RCSB], [http://www.ebi.ac.uk/pdbsum/5w45 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w45 ProSAT]</span></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=5w45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w45 OCA], [https://pdbe.org/5w45 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w45 RCSB], [https://www.ebi.ac.uk/pdbsum/5w45 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w45 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 ==
@@ Line 20: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Arutiunian, V]]
+[[Category: Homo sapiens]]
-[[Category: Chen, X J]]
+[[Category: Large Structures]]
-[[Category: Ito, F]]
+[[Category: Arutiunian V]]
-[[Category: Li, S X]]
+[[Category: Chen XS]]
-[[Category: Wolfe, A]]
+[[Category: Ito F]]
-[[Category: Xiao, X]]
+[[Category: Li SX]]
-[[Category: Yang, H J]]
+[[Category: Wolfe A]]
-[[Category: Zirkle, B]]
+[[Category: Xiao X]]
-[[Category: Dna binding protein]]
+[[Category: Yang HJ]]
-[[Category: Mutase]]
+[[Category: Zirkle B]]

5w45

From Proteopedia

Current revision

Crystal structure of APOBEC3H

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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