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4xxo

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Revision as of 12:17, 6 November 2017

Crystal Structure of Human APOBEC3A

Structural highlights

4xxo is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	APOBEC3A (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ABC3A_HUMAN] DNA deaminase (cytidine deaminase) with restriction activity against viruses, foreign DNA and mobility of retrotransposons. Exhibits antiviral activity against adeno-associated virus (AAV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. Selectively targets single-stranded DNA and can deaminate both methylcytosine and cytosine in foreign DNA. Can induce somatic hypermutation in the nuclear and mitochondrial DNA. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

Publication Abstract from PubMed

Deaminase activity mediated by the human APOBEC3 family of proteins contributes to genomic instability and cancer. APOBEC3A is by far the most active in this family and can cause rapid cell death when overexpressed, but in general how the activity of APOBEC3s is regulated on a molecular level is unclear. In this study, the biochemical and structural basis of APOBEC3A substrate binding and specificity is elucidated. We find that specific binding of single-stranded DNA is regulated by the cooperative dimerization of APOBEC3A. The crystal structure elucidates this homodimer as a symmetric domain swap of the N-terminal residues. This dimer interface provides insights into how cooperative protein-protein interactions may affect function in the APOBEC3 enzymes and provides a potential scaffold for strategies aimed at reducing their mutation load.

The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization.,Bohn MF, Shandilya SM, Silvas TV, Nalivaika EA, Kouno T, Kelch BA, Ryder SP, Kurt-Yilmaz N, Somasundaran M, Schiffer CA Structure. 2015 May 5;23(5):903-11. doi: 10.1016/j.str.2015.03.016. Epub 2015 Apr, 23. PMID:25914058^[13]

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

References

↑ Madsen P, Anant S, Rasmussen HH, Gromov P, Vorum H, Dumanski JP, Tommerup N, Collins JE, Wright CL, Dunham I, MacGinnitie AJ, Davidson NO, Celis JE. Psoriasis upregulated phorbolin-1 shares structural but not functional similarity to the mRNA-editing protein apobec-1. J Invest Dermatol. 1999 Aug;113(2):162-9. PMID:10469298 doi:10.1046/j.1523-1747.1999.00682.x
↑ 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
↑ 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
↑ Narvaiza I, Linfesty DC, Greener BN, Hakata Y, Pintel DJ, Logue E, Landau NR, Weitzman MD. Deaminase-independent inhibition of parvoviruses by the APOBEC3A cytidine deaminase. PLoS Pathog. 2009 May;5(5):e1000439. doi: 10.1371/journal.ppat.1000439. Epub 2009, May 22. PMID:19461882 doi:10.1371/journal.ppat.1000439
↑ Thielen BK, McNevin JP, McElrath MJ, Hunt BV, Klein KC, Lingappa JR. Innate immune signaling induces high levels of TC-specific deaminase activity in primary monocyte-derived cells through expression of APOBEC3A isoforms. J Biol Chem. 2010 Sep 3;285(36):27753-66. doi: 10.1074/jbc.M110.102822. Epub 2010, Jul 8. PMID:20615867 doi:10.1074/jbc.M110.102822
↑ 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
↑ Guo JU, Su Y, Zhong C, Ming GL, Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011 Apr 29;145(3):423-34. doi: 10.1016/j.cell.2011.03.022. Epub 2011 Apr, 14. PMID:21496894 doi:10.1016/j.cell.2011.03.022
↑ Landry S, Narvaiza I, Linfesty DC, Weitzman MD. APOBEC3A can activate the DNA damage response and cause cell-cycle arrest. EMBO Rep. 2011 May;12(5):444-50. doi: 10.1038/embor.2011.46. Epub 2011 Apr 1. PMID:21460793 doi:10.1038/embor.2011.46
↑ 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
↑ Suspene R, Aynaud MM, Guetard D, Henry M, Eckhoff G, Marchio A, Pineau P, Dejean A, Vartanian JP, Wain-Hobson S. Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4858-63. doi:, 10.1073/pnas.1009687108. Epub 2011 Mar 2. PMID:21368204 doi:10.1073/pnas.1009687108
↑ Carpenter MA, Li M, Rathore A, Lackey L, Law EK, Land AM, Leonard B, Shandilya SM, Bohn MF, Schiffer CA, Brown WL, Harris RS. Methylcytosine and normal cytosine deamination by the foreign DNA restriction enzyme APOBEC3A. J Biol Chem. 2012 Oct 5;287(41):34801-8. doi: 10.1074/jbc.M112.385161. Epub 2012 , Aug 15. PMID:22896697 doi:10.1074/jbc.M112.385161
↑ 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
↑ Bohn MF, Shandilya SM, Silvas TV, Nalivaika EA, Kouno T, Kelch BA, Ryder SP, Kurt-Yilmaz N, Somasundaran M, Schiffer CA. The ssDNA Mutator APOBEC3A Is Regulated by Cooperative Dimerization. Structure. 2015 May 5;23(5):903-11. doi: 10.1016/j.str.2015.03.016. Epub 2015 Apr, 23. PMID:25914058 doi:http://dx.doi.org/10.1016/j.str.2015.03.016

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/4xxo"

@@ Line 3: / Line 3: @@
 <StructureSection load='4xxo' size='340' side='right' caption='[[4xxo]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xxo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xxo]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXO FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APOBEC3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4xxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxo OCA], [http://pdbe.org/4xxo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xxo RCSB], [http://www.ebi.ac.uk/pdbsum/4xxo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxo ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Bohn, M F]]
 [[Category: Schiffer, C A]]

4xxo

From Proteopedia

Revision as of 12:17, 6 November 2017

Crystal Structure of Human APOBEC3A

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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