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Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein
The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response and have broad activity against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity fact...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950479/ https://www.ncbi.nlm.nih.gov/pubmed/24345943 http://dx.doi.org/10.1038/nchem.1795 |
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author | Chaurasiya, Kathy R. McCauley, Micah J. Wang, Wei Qualley, Dominic F. Wu, Tiyun Kitamura, Shingo Geertsema, Hylkje Chan, Denise S.B. Hertz, Amber Iwatani, Yasumasa Levin, Judith G. Musier-Forsyth, Karin Rouzina, Ioulia Williams, Mark C. |
author_facet | Chaurasiya, Kathy R. McCauley, Micah J. Wang, Wei Qualley, Dominic F. Wu, Tiyun Kitamura, Shingo Geertsema, Hylkje Chan, Denise S.B. Hertz, Amber Iwatani, Yasumasa Levin, Judith G. Musier-Forsyth, Karin Rouzina, Ioulia Williams, Mark C. |
author_sort | Chaurasiya, Kathy R. |
collection | PubMed |
description | The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response and have broad activity against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalyzed DNA elongation. Here we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription. |
format | Online Article Text |
id | pubmed-3950479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-39504792014-07-01 Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein Chaurasiya, Kathy R. McCauley, Micah J. Wang, Wei Qualley, Dominic F. Wu, Tiyun Kitamura, Shingo Geertsema, Hylkje Chan, Denise S.B. Hertz, Amber Iwatani, Yasumasa Levin, Judith G. Musier-Forsyth, Karin Rouzina, Ioulia Williams, Mark C. Nat Chem Article The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response and have broad activity against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalyzed DNA elongation. Here we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription. 2013-11-24 2014-01 /pmc/articles/PMC3950479/ /pubmed/24345943 http://dx.doi.org/10.1038/nchem.1795 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Chaurasiya, Kathy R. McCauley, Micah J. Wang, Wei Qualley, Dominic F. Wu, Tiyun Kitamura, Shingo Geertsema, Hylkje Chan, Denise S.B. Hertz, Amber Iwatani, Yasumasa Levin, Judith G. Musier-Forsyth, Karin Rouzina, Ioulia Williams, Mark C. Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein |
title | Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein |
title_full | Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein |
title_fullStr | Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein |
title_full_unstemmed | Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein |
title_short | Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein |
title_sort | oligomerization transforms human apobec3g from an efficient enzyme to a slowly dissociating nucleic acid binding protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950479/ https://www.ncbi.nlm.nih.gov/pubmed/24345943 http://dx.doi.org/10.1038/nchem.1795 |
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