Structural Model for Deoxycytidine Deamination Mechanisms of the HIV-1 Inactivation Enzyme APOBEC3G*♦

@article{Chelico2010StructuralMF,
  title={Structural Model for Deoxycytidine Deamination Mechanisms of the HIV-1 Inactivation Enzyme APOBEC3G*♦},
  author={L. Chelico and Courtney Prochnow and D. Erie and Xiaojiang S. Chen and M. Goodman},
  journal={The Journal of Biological Chemistry},
  year={2010},
  volume={285},
  pages={16195 - 16205}
}
APOBEC3G (Apo3G) is a single-stranded DNA-dependent deoxycytidine deaminase, which, in the absence of the human immunodeficiency virus (HIV) viral infectivity factor, is encapsulated into HIV virions. Subsequently, Apo3G triggers viral inactivation by processively deaminating C→U, with 3′→5′ polarity, on nascent minus-strand cDNA. Apo3G has a catalytically inactive N-terminal CD1 domain and an active C-terminal CD2 domain. Apo3G exists as monomers, dimers, tetramers, and higher order oligomers… Expand
Dimerization regulates both deaminase-dependent and deaminase-independent HIV-1 restriction by APOBEC3G
TLDR
It is shown that APOBEC3G binds single-stranded DNA as an active deaminase monomer, subsequently forming catalytic-inactive dimers that block reverse transcriptase-mediated DNA synthesis and may inhibit reverse transcription. Expand
Intensity of Deoxycytidine Deamination of HIV-1 Proviral DNA by the Retroviral Restriction Factor APOBEC3G Is Mediated by the Noncatalytic Domain*
TLDR
The data demonstrate that the balance between the jumping and sliding of Apo3G is needed for efficient mutational inactivation of HIV-1 and reveal a functionality for ApO3G oligomers in deamination and provide the first biochemical characterization of the clinical mutant H186R. Expand
Cytidine deaminase efficiency of the lentiviral viral restriction factor APOBEC3C correlates with dimerization
TLDR
It is demonstrated that chimpanzee and gorilla A3C have approximately equivalent activity to human A 3C I188 and that chimpanzees and gorilla a3C form dimers at the same interface as human A2C S188I, but through different amino acids. Expand
RNA-Mediated Dimerization of the Human Deoxycytidine Deaminase APOBEC3H Influences Enzyme Activity and Interaction with Nucleic Acids.
TLDR
The biochemical analysis demonstrates that RNA binding is integral to APOBEC3H function, and determines how the dimerization mechanism influenced interactions with and activity on ssDNA. Expand
Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G
TLDR
A model in which only one RNA-binding mode is critical for virion packaging and restriction of HIV-1 by A3G is supported, which provides insight into domain organization, multimerization, RNA binding, and viral restriction. Expand
Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G
APOBEC3G, a member of the double-domain cytidine deaminase (CD) APOBEC, binds RNA to package into virions and restrict HIV-1 through deamination-dependent or deamination-independent inhibition.Expand
Mechanism of Enhanced HIV Restriction by Virion Coencapsidated Cytidine Deaminases APOBEC3F and APOBEC3G
TLDR
Evidence is provided for an A3F/G hetero-oligomeric A3 with unique properties compared to each individual counterpart in the absence of RNA which has increased efficiency of virus hypermutation. Expand
HIV restriction factor APOBEC3G binds in multiple steps and conformations to search and deaminate single-stranded DNA
TLDR
Oligomerization of A3G stabilizes ssDNA binding but inhibits the CTD’s search function, which explains A3Gs ability to efficiently deaminate numerous sites across a 10,000 base viral genome during the reverse transcription process. Expand
Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein
TLDR
It is shown that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode, and an oligomerization-deficient APOBec3G mutant did not exhibit a slow off rate. Expand
Single-stranded DNA Scanning and Deamination by APOBEC3G Cytidine Deaminase at Single Molecule Resolution*♦
TLDR
The specific issue of deamination asymmetry within the general context of ssDNA scanning mechanisms is addressed and it is shown that Apo3G scanning trajectories, ssDNA contraction, and deamination efficiencies depend on motif sequence, location, and ionic strength. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 53 REFERENCES
RNA-Dependent Oligomerization of APOBEC3G Is Required for Restriction of HIV-1
TLDR
It is proposed that occupation of the positively charged pocket by RNA promotes A3G oligomerization, packaging into virions and antiviral function. Expand
A Model for Oligomeric Regulation of APOBEC3G Cytosine Deaminase-dependent Restriction of HIV*
TLDR
It is suggested that diverse A3G oligomerization modes contribute to the human immunodeficiency virus, type 1, proviral DNA mutational bias. Expand
Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G
TLDR
The structure of the APOBEC3G catalytic domain will help to understand functions of other family members and interactions that occur with pathogenic proteins such as HIV-1 Vif and Escherichia coli-based activity assays. Expand
The APOBEC-2 crystal structure and functional implications for the deaminase AID
TLDR
The crystal structure of APO2 is reported and it is shown that AID deamination activity is impaired by mutations predicted to interfere with oligomerization and substrate access, resulting in defective antibody maturation. Expand
APOBEC3G Subunits Self-associate via the C-terminal Deaminase Domain*
TLDR
Co-immunoprecipitation and in-cell quenched fluorescence resonance energy transfer assays reveal that hA3G forms RNA-independent oligomers through interactions within its C terminus, corroborate the small angle x-ray scattering structural model and are instructive for development of high throughput screens that target specific domains and their functions to identify HIV/AIDS therapeutics. Expand
The Interaction between HIV-1 Gag and APOBEC3G*
TLDR
Evidence against an RNA bridge facilitating the Gag/APOBEC3G interaction includes data indicating that 1) the incorporation of APOB EC3G occurs independently of viral genomic RNA, 2) a Gag-APOBec3G complex is immunoprecipitated from cell lysate after RNase treatment, and 3) the zinc coordination motif, rather than the regions flanking this motif, have been implicated in RNA binding in another family member, APOBEC1. Expand
Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome
TLDR
It is reported here that minus-strand deamination occurred over the length of the virus genome, preferentially at CCCA sequences, with a graded frequency in the 5′→3′ direction. Expand
Complementary function of the two catalytic domains of APOBEC3G.
TLDR
A model in which CD1 mediates encapsidation and RNA binding while CD2 mediates cytidine deaminase activity is suggested, which suggests that HTLV-I was relatively resistant to the antiviral effects of encapsidated APOBEC3G. Expand
Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications
TLDR
The high-resolution crystal structure of the carboxy-terminal deaminase domain of APOBEC3G (APOBec3G-CD2) purified from Escherichia coli is reported, and residues involved in substrate specificity, single-stranded DNA binding and deaminases activity are identified. Expand
Dissecting APOBEC3G Substrate Specificity by Nucleoside Analog Interference*
TLDR
Nucleoside analog interference mapping is used to probe A3G-DNA interactions throughout the enzyme-substrate complex as well as to determine which DNA structural features determine substrate specificity, indicating that multiple components of nucleosides within the consensus sequence are important for substrate recognition by A2G, whereas deamination interference by analog substitution outside this region is minimal. Expand
...
1
2
3
4
5
...