6k3j

From Proteopedia

(Difference between revisions)

Revision as of 05:38, 12 June 2019

Solution structure of APOBEC3G-CD2 with ssDNA, Product A

Structural highlights

6k3j is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

Publication Abstract from PubMed

Human APOBEC3G (A3G) is a cytidine deaminase, which inhibits the replication of human immunodeficiency virus-1 by deaminating cytidine at 3'-end in target motif 5'-CCCA-3' in viral cDNA during the reverse transcription. It can in vitro deaminate two consecutive cytidines in a 3'->5' order. Although the crystal structure of A3G catalytic domain (A3G-CD2) variant with DNA was reported, it's still unknown why the residues involved in DNA binding and enzymatic deamination are distributed widely on its surface. To address this, we introduced steric iodine into C-5 position of cytidine (dC6I) in substrate 5'-ATTC4C5C6IA7ATT-3' DNA (abbreviated as TCCC6I). This modification significantly switches the sequence preference of A3G catalytic deamination from 5'-CCC-3' into 5'-TCC-3', although slight dC6I deamination was observed. Solution structures of A3G-CD2 in complex with deamination products TCUC6I DNA and TCUU6I DNA were resolved, which indicate that substrate DNA interacts with A3G-CD2 in two binding modes (termed as TCC and CCC). The dC6 deamination rate is dependent on the type of the most 5'-end base in the motif 5'-XCCA-3' (X=C,T,A or G). CCC mode is in favour of dC6 deamination, while TCC mode avails dC5 deamination. These studies present extensively structural basis to design inhibitors to impede the evolvability of viruses.

Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA.,Yan X, Lan W, Wang C, Cao C Chem Asian J. 2019 May 22. doi: 10.1002/asia.201900480. PMID:31116511^[13]

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

References

↑ Kao S, Khan MA, Miyagi E, Plishka R, Buckler-White A, Strebel K. The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity. J Virol. 2003 Nov;77(21):11398-407. PMID:14557625
↑ Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002 Aug 8;418(6898):646-50. Epub 2002 Jul 14. PMID:12167863 doi:10.1038/nature00939
↑ Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature. 2003 Jul 3;424(6944):99-103. Epub 2003 May 28. PMID:12808466 doi:10.1038/nature01709
↑ Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH. DNA deamination mediates innate immunity to retroviral infection. Cell. 2003 Jun 13;113(6):803-9. PMID:12809610
↑ Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L. The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature. 2003 Jul 3;424(6944):94-8. Epub 2003 May 28. PMID:12808465 doi:10.1038/nature01707
↑ Mariani R, Chen D, Schrofelbauer B, Navarro F, Konig R, Bollman B, Munk C, Nymark-McMahon H, Landau NR. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell. 2003 Jul 11;114(1):21-31. PMID:12859895
↑ Shindo K, Takaori-Kondo A, Kobayashi M, Abudu A, Fukunaga K, Uchiyama T. The enzymatic activity of CEM15/Apobec-3G is essential for the regulation of the infectivity of HIV-1 virion but not a sole determinant of its antiviral activity. J Biol Chem. 2003 Nov 7;278(45):44412-6. Epub 2003 Sep 11. PMID:12970355 doi:http://dx.doi.org/10.1074/jbc.C300376200
↑ Sheehy AM, Gaddis NC, Malim MH. The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med. 2003 Nov;9(11):1404-7. Epub 2003 Oct 5. PMID:14528300 doi:10.1038/nm945
↑ Turelli P, Mangeat B, Jost S, Vianin S, Trono D. Inhibition of hepatitis B virus replication by APOBEC3G. Science. 2004 Mar 19;303(5665):1829. PMID:15031497 doi:10.1126/science.1092066
↑ Chen H, Lilley CE, Yu Q, Lee DV, Chou J, Narvaiza I, Landau NR, Weitzman MD. APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons. Curr Biol. 2006 Mar 7;16(5):480-5. PMID:16527742 doi:10.1016/j.cub.2006.01.031
↑ Bulliard Y, Narvaiza I, Bertero A, Peddi S, Rohrig UF, Ortiz M, Zoete V, Castro-Diaz N, Turelli P, Telenti A, Michielin O, Weitzman MD, Trono D. Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities. J Virol. 2011 Feb;85(4):1765-76. doi: 10.1128/JVI.01651-10. Epub 2010 Dec 1. PMID:21123384 doi:10.1128/JVI.01651-10
↑ Chen KM, Harjes E, Gross PJ, Fahmy A, Lu Y, Shindo K, Harris RS, Matsuo H. Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature. 2008 Mar 6;452(7183):116-9. Epub 2008 Feb 20. PMID:18288108 doi:10.1038/nature06638
↑ Yan X, Lan W, Wang C, Cao C. Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA. Chem Asian J. 2019 May 22. doi: 10.1002/asia.201900480. PMID:31116511 doi:http://dx.doi.org/10.1002/asia.201900480

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/6k3j"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6k3j is ON HOLD
+==Solution structure of APOBEC3G-CD2 with ssDNA, Product A==
+<StructureSection load='6k3j' size='340' side='right'caption='[[6k3j]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6k3j]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K3J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6K3J 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>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5IU:5-IODO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>5IU</scene>, <scene name='pdbligand=DU:2-DEOXYURIDINE-5-MONOPHOSPHATE'>DU</scene></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=6k3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k3j OCA], [http://pdbe.org/6k3j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6k3j RCSB], [http://www.ebi.ac.uk/pdbsum/6k3j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6k3j ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://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 APOBEC3G (A3G) is a cytidine deaminase, which inhibits the replication of human immunodeficiency virus-1 by deaminating cytidine at 3'-end in target motif 5'-CCCA-3' in viral cDNA during the reverse transcription. It can in vitro deaminate two consecutive cytidines in a 3'-&gt;5' order. Although the crystal structure of A3G catalytic domain (A3G-CD2) variant with DNA was reported, it's still unknown why the residues involved in DNA binding and enzymatic deamination are distributed widely on its surface. To address this, we introduced steric iodine into C-5 position of cytidine (dC6I) in substrate 5'-ATTC4C5C6IA7ATT-3' DNA (abbreviated as TCCC6I). This modification significantly switches the sequence preference of A3G catalytic deamination from 5'-CCC-3' into 5'-TCC-3', although slight dC6I deamination was observed. Solution structures of A3G-CD2 in complex with deamination products TCUC6I DNA and TCUU6I DNA were resolved, which indicate that substrate DNA interacts with A3G-CD2 in two binding modes (termed as TCC and CCC). The dC6 deamination rate is dependent on the type of the most 5'-end base in the motif 5'-XCCA-3' (X=C,T,A or G). CCC mode is in favour of dC6 deamination, while TCC mode avails dC5 deamination. These studies present extensively structural basis to design inhibitors to impede the evolvability of viruses.
-Authors:
+Structural Investigations on the Interactions between Cytidine Deaminase Human APOBEC3G and DNA.,Yan X, Lan W, Wang C, Cao C Chem Asian J. 2019 May 22. doi: 10.1002/asia.201900480. PMID:31116511<ref>PMID:31116511</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6k3j" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Cao, C]]
+[[Category: Lan, W]]
+[[Category: Wang, C]]
+[[Category: Yan, X]]
+[[Category: Apobec3g]]
+[[Category: Dna cytidine deaminase complex with dna]]
+[[Category: Hydrolase-dna complex]]

6k3j

From Proteopedia

Revision as of 05:38, 12 June 2019

Solution structure of APOBEC3G-CD2 with ssDNA, Product A

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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