Show simple item record

dc.contributor.authorMaiti, Atanu
dc.contributor.authorMyint, Wazo
dc.contributor.authorKanai, Tapan
dc.contributor.authorDelviks-Frankenberry, Krista
dc.contributor.authorSierra Rodriguez, Christina
dc.contributor.authorPathak, Vinay K.
dc.contributor.authorSchiffer, Celia A.
dc.contributor.authorMatsuo, Hiroshi
dc.date2022-08-11T08:09:50.000
dc.date.accessioned2022-08-23T16:45:38Z
dc.date.available2022-08-23T16:45:38Z
dc.date.issued2018-06-25
dc.date.submitted2018-08-16
dc.identifier.citation<p>Nat Commun. 2018 Jun 25;9(1):2460. doi: 10.1038/s41467-018-04872-8. <a href="https://doi.org/10.1038/s41467-018-04872-8">Link to article on publisher's site</a></p>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/s41467-018-04872-8
dc.identifier.pmid29941968
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40720
dc.description.abstractThe human APOBEC3G protein is a cytidine deaminase that generates cytidine to deoxy-uridine mutations in single-stranded DNA (ssDNA), and capable of restricting replication of HIV-1 by generating mutations in viral genome. The mechanism by which APOBEC3G specifically deaminates 5'-CC motifs has remained elusive since structural studies have been hampered due to apparently weak ssDNA binding of the catalytic domain of APOBEC3G. We overcame the problem by generating a highly active variant with higher ssDNA affinity. Here, we present the crystal structure of this variant complexed with a ssDNA substrate at 1.86 A resolution. This structure reveals atomic-level interactions by which APOBEC3G recognizes a functionally-relevant 5'-TCCCA sequence. This complex also reveals a key role of W211 in substrate recognition, implicating a similar recognition in activation-induced cytidine deaminase (AID) with a conserved tryptophan.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29941968&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectEnzymes and Coenzymes
dc.subjectGenetic Phenomena
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.subjectStructural Biology
dc.subjectViruses
dc.titleCrystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume9
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4535&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3523
dc.identifier.contextkey12668450
refterms.dateFOA2022-08-23T16:45:38Z
html.description.abstract<p>The human APOBEC3G protein is a cytidine deaminase that generates cytidine to deoxy-uridine mutations in single-stranded DNA (ssDNA), and capable of restricting replication of HIV-1 by generating mutations in viral genome. The mechanism by which APOBEC3G specifically deaminates 5'-CC motifs has remained elusive since structural studies have been hampered due to apparently weak ssDNA binding of the catalytic domain of APOBEC3G. We overcame the problem by generating a highly active variant with higher ssDNA affinity. Here, we present the crystal structure of this variant complexed with a ssDNA substrate at 1.86 A resolution. This structure reveals atomic-level interactions by which APOBEC3G recognizes a functionally-relevant 5'-TCCCA sequence. This complex also reveals a key role of W211 in substrate recognition, implicating a similar recognition in activation-induced cytidine deaminase (AID) with a conserved tryptophan.</p>
dc.identifier.submissionpathoapubs/3523
dc.contributor.departmentSchiffer Lab
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages2460


Files in this item

Thumbnail
Name:
s41467_018_04872_8.pdf
Size:
1.642Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

© The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.