5tkm

From Proteopedia

(Difference between revisions)

Revision as of 12:33, 25 December 2019

Crystal structure of human APOBEC3B N-terminal Domain

Structural highlights

5tkm 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:	APOBEC3B (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ABC3B_HUMAN] DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. 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. 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. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single-or double-stranded RNA. Exhibits antiviral activity against simian immunodeficiency virus (SIV), hepatitis B virus (HBV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

The catalytic activity of human cytidine deaminase APOBEC3B (A3B) has been correlated with kataegic mutational patterns within multiple cancer types. The molecular basis of how the N-terminal non-catalytic CD1 regulates the catalytic activity and consequently, biological function of A3B remains relatively unknown. Here, we report the crystal structure of a soluble human A3B-CD1 variant and delineate several structural elements of CD1 involved in molecular assembly, nucleic acid interactions and catalytic regulation of A3B. We show that (i) A3B expressed in human cells exists in hypoactive high-molecular-weight (HMW) complexes, which can be activated without apparent dissociation into low-molecular-weight (LMW) species after RNase A treatment. (ii) Multiple surface hydrophobic residues of CD1 mediate the HMW complex assembly and affect the catalytic activity, including one tryptophan residue W127 that likely acts through regulating nucleic acid binding. (iii) One of the highly positively charged surfaces on CD1 is involved in RNA-dependent attenuation of A3B catalysis. (iv) Surface hydrophobic residues of CD1 are involved in heterogeneous nuclear ribonucleoproteins (hnRNPs) binding to A3B. The structural and biochemical insights described here suggest that unique structural features on CD1 regulate the molecular assembly and catalytic activity of A3B through distinct mechanisms.

Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation.,Xiao X, Yang H, Arutiunian V, Fang Y, Besse G, Morimoto C, Zirkle B, Chen XS Nucleic Acids Res. 2017 Jul 7;45(12):7494-7506. doi: 10.1093/nar/gkx362. PMID:28575276^[7]

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

References

↑ 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
↑ Yu Q, Chen D, Konig R, Mariani R, Unutmaz D, Landau NR. APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J Biol Chem. 2004 Dec 17;279(51):53379-86. Epub 2004 Oct 4. PMID:15466872 doi:http://dx.doi.org/10.1074/jbc.M408802200
↑ Rose KM, Marin M, Kozak SL, Kabat D. Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G. AIDS Res Hum Retroviruses. 2005 Jul;21(7):611-9. PMID:16060832 doi:http://dx.doi.org/10.1089/aid.2005.21.611
↑ 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
↑ 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
↑ 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
↑ Xiao X, Yang H, Arutiunian V, Fang Y, Besse G, Morimoto C, Zirkle B, Chen XS. Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation. Nucleic Acids Res. 2017 Jul 7;45(12):7494-7506. doi: 10.1093/nar/gkx362. PMID:28575276 doi:http://dx.doi.org/10.1093/nar/gkx362

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/5tkm"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human APOBEC3B N-terminal Domain==
-<StructureSection load='5tkm' size='340' side='right' caption='[[5tkm]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='5tkm' size='340' side='right'caption='[[5tkm]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tkm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TKM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tkm]] 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=5TKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TKM 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APOBEC3B ([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=5tkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tkm OCA], [http://pdbe.org/5tkm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tkm RCSB], [http://www.ebi.ac.uk/pdbsum/5tkm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tkm ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Arutiunian, V]]
 [[Category: Besse, G]]

5tkm

From Proteopedia

Revision as of 12:33, 25 December 2019

Crystal structure of human APOBEC3B N-terminal Domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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