Extensive mutagenesis experiments corroborate a structural model for the DNA deaminase domain of APOBEC3G

Kuan Ming Chen; Natalia Martemyanova; Yongjian Lu; Keisuke Shindo; Hiroshi Matsuo; Reuben S. Harris

doi:10.1016/j.febslet.2007.08.076

Extensive mutagenesis experiments corroborate a structural model for the DNA deaminase domain of APOBEC3G

Kuan Ming Chen, Natalia Martemyanova, Yongjian Lu, Keisuke Shindo, Hiroshi Matsuo, Reuben S. Harris

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

APOBEC3G is a single-strand DNA cytosine deaminase capable of blocking retrovirus and retrotransposon replication. APOBEC3G has two conserved zinc-coordinating motifs but only one is required for catalysis. Here, deletion analyses revealed that the minimal catalytic domain consists of residues 198-384. Size exclusion assays indicated that this protein is monomeric. Many (31/69) alanine substitution derivatives of APOBEC3G198-384 retained significant to full levels of activity. These data corroborated an APOBEC2-based structural model for the catalytic domain of APOBEC3G indicating that most non-essential residues are solvent accessible and most essential residues cluster within the protein core.

Original language	English (US)
Pages (from-to)	4761-4766
Number of pages	6
Journal	FEBS Letters
Volume	581
Issue number	24
DOIs	https://doi.org/10.1016/j.febslet.2007.08.076
State	Published - Oct 2 2007
Externally published	Yes

Keywords

APOBEC3G
DNA cytosine deamination
DNA editing
Hypermutation

ASJC Scopus subject areas

Genetics
Molecular Biology
Biophysics
Structural Biology
Biochemistry
Cell Biology

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10.1016/j.febslet.2007.08.076

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title = "Extensive mutagenesis experiments corroborate a structural model for the DNA deaminase domain of APOBEC3G",

abstract = "APOBEC3G is a single-strand DNA cytosine deaminase capable of blocking retrovirus and retrotransposon replication. APOBEC3G has two conserved zinc-coordinating motifs but only one is required for catalysis. Here, deletion analyses revealed that the minimal catalytic domain consists of residues 198-384. Size exclusion assays indicated that this protein is monomeric. Many (31/69) alanine substitution derivatives of APOBEC3G198-384 retained significant to full levels of activity. These data corroborated an APOBEC2-based structural model for the catalytic domain of APOBEC3G indicating that most non-essential residues are solvent accessible and most essential residues cluster within the protein core.",

keywords = "APOBEC3G, DNA cytosine deamination, DNA editing, Hypermutation",

author = "Chen, {Kuan Ming} and Natalia Martemyanova and Yongjian Lu and Keisuke Shindo and Hiroshi Matsuo and Harris, {Reuben S.}",

note = "Funding Information: This work was supported by NIH Grants AI064046 (RSH) and AI073167 (HM) and by the University of Minnesota{\textquoteright}s Leukemia Research Fund (RSH) and Grant-in-Aid Program (HM). R.S.H. is a Searle Scholar and a University of Minnesota McKnight Land Grant Assistant Professor. We thank A. Briggs, P. Gross and Y. Sham for technical assistance, Harris and Matsuo laboratory members for helpful discussions and the University of Minnesota AGAC and SCI for DNA sequencing and computational resources, respectively. ",

year = "2007",

month = oct,

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doi = "10.1016/j.febslet.2007.08.076",

language = "English (US)",

volume = "581",

pages = "4761--4766",

journal = "FEBS Letters",

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publisher = "John Wiley and Sons Inc.",

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T1 - Extensive mutagenesis experiments corroborate a structural model for the DNA deaminase domain of APOBEC3G

AU - Chen, Kuan Ming

AU - Martemyanova, Natalia

AU - Lu, Yongjian

AU - Shindo, Keisuke

AU - Matsuo, Hiroshi

AU - Harris, Reuben S.

N1 - Funding Information: This work was supported by NIH Grants AI064046 (RSH) and AI073167 (HM) and by the University of Minnesota’s Leukemia Research Fund (RSH) and Grant-in-Aid Program (HM). R.S.H. is a Searle Scholar and a University of Minnesota McKnight Land Grant Assistant Professor. We thank A. Briggs, P. Gross and Y. Sham for technical assistance, Harris and Matsuo laboratory members for helpful discussions and the University of Minnesota AGAC and SCI for DNA sequencing and computational resources, respectively.

PY - 2007/10/2

Y1 - 2007/10/2

N2 - APOBEC3G is a single-strand DNA cytosine deaminase capable of blocking retrovirus and retrotransposon replication. APOBEC3G has two conserved zinc-coordinating motifs but only one is required for catalysis. Here, deletion analyses revealed that the minimal catalytic domain consists of residues 198-384. Size exclusion assays indicated that this protein is monomeric. Many (31/69) alanine substitution derivatives of APOBEC3G198-384 retained significant to full levels of activity. These data corroborated an APOBEC2-based structural model for the catalytic domain of APOBEC3G indicating that most non-essential residues are solvent accessible and most essential residues cluster within the protein core.

AB - APOBEC3G is a single-strand DNA cytosine deaminase capable of blocking retrovirus and retrotransposon replication. APOBEC3G has two conserved zinc-coordinating motifs but only one is required for catalysis. Here, deletion analyses revealed that the minimal catalytic domain consists of residues 198-384. Size exclusion assays indicated that this protein is monomeric. Many (31/69) alanine substitution derivatives of APOBEC3G198-384 retained significant to full levels of activity. These data corroborated an APOBEC2-based structural model for the catalytic domain of APOBEC3G indicating that most non-essential residues are solvent accessible and most essential residues cluster within the protein core.

KW - APOBEC3G

KW - DNA cytosine deamination

KW - DNA editing

KW - Hypermutation

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SN - 0014-5793

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JO - FEBS Letters

JF - FEBS Letters

IS - 24

ER -

Extensive mutagenesis experiments corroborate a structural model for the DNA deaminase domain of APOBEC3G

Abstract

Keywords

ASJC Scopus subject areas

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