{"id":609,"date":"2015-07-29T11:14:15","date_gmt":"2015-07-29T11:14:15","guid":{"rendered":"http:\/\/www.virologyhighlights.com\/?p=609"},"modified":"2018-05-25T08:27:46","modified_gmt":"2018-05-25T08:27:46","slug":"unexpected-protein-domain-interactions-affect-the-target-specificity-of-human-apobec3g1","status":"publish","type":"post","link":"https:\/\/www.elsevierblogs.com\/virology\/unexpected-protein-domain-interactions-affect-the-target-specificity-of-human-apobec3g1\/","title":{"rendered":"Unexpected Protein Domain Interactions Affect the Target Specificity of Human APOBEC3G"},"content":{"rendered":"

RNA-binding residues in the N-terminus of APOBEC3G influence its DNA sequence specificity and retrovirus restriction efficiency<\/strong><\/h2>\n

Read the full article on ScienceDirect<\/a><\/h3>\n

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APOBEC3 (A3) proteins are expressed in the cells of placental mammals. They have an important role in providing an effective innate immune defense against retroviral infection and zoonosis. Their claim to fame happened when it was revealed that a number of A3 proteins are specifically targeted for degradation by the Vif protein encoded by the human immunodeficiency virus (HIV). Without Vif, HIV would be unable to spread because of A3 proteins. A3 are enzymes that convert cytosine in single-stranded DNA into uracil, thereby generating C-to-U mutations.\u00a0Although most A3 proteins are cytosolic and act outside the nucleus of the cell, some A3 proteins have now been identified as the cause of cancer causing mutations. It is for these reasons that there is a significant interest in understanding the fine details of how A3 proteins work, how they are regulated and how they select their DNA target sites.<\/h4>\n

<\/h4>\n

For a number of years, we have been interested in looking at how the most potent member of the human A3 family, APOBEC3G (A3G), binds to RNA. Although A3G strictly deaminates single-stranded DNA, it also binds to RNA causing it to assemble into high molecular mass complexes in which the protein is catalytically inactive and unable to get packaged into budding retroviruses. This phenomenon is particularly emphasized in dividing cells. So it seemed to us that certain cytoplasmic RNAs negatively regulate the activity of A3G. Hence, we wondered if the potency of A3G would increase if it could no longer bind RNA. What we found, however, was that mutations that affect RNA binding also reduce the antiviral activity of the protein. In this study, we set out to characterize the distinctive features of an RNA-binding mutant of A3G containing a double substitution located in the N-terminal domain (NTD) of the protein (W94A\/W127A).<\/h4>\n

 <\/p>\n

Many of our findings were unexpected, however, the most intriguing result of all was that the preferred deamination sequence was strikingly altered from 5\u2019CC to 5\u2019TC. All human A3 proteins except A3G have a strong 5\u2019TC preference. This came as a surprise because the main residues involved in DNA-binding and deamination are located in the C-terminal domain (CTD). Although crystal structures are independently known for both the NTD and CTD, the crystal of the full-length protein has still not been solved. Our results suggest that the NTD strongly influences how the CTD interacts with the DNA substrate and identifies preferred deamination sites.<\/h4>\n

\"Figure\"<\/a><\/p>\n

Figure legend<\/h3>\n

The non-catalytic NTD of A3G influences the target DNA specificity of the enzyme. A) Graphical representation of the human A3G protein with its various functional domains. Red arrows indicate the positions of residues W94 and W127. B)\u00a0Both wild type A3G and the RNA-binding deficient mutant W94A\/W127A have a cytoplasmic distribution and form defined foci. C) The W94A\/W127A double substitution modifies the enzyme\u2019s target specificity from 5\u2019CC to 5\u2019TC on both HIV-1 and E.coli DNA.<\/h4>\n

 <\/p>\n

Introducing the authors<\/strong><\/h3>\n

\"Authors\"<\/a>
\nKasandra B\u00e9langer and Marc-Andr\u00e9 Langlois<\/h4>\n

 <\/p>\n

About the Research<\/strong><\/h3>\n

RNA-binding residues in the N-terminus of APOBEC3G influence its DNA sequence specificity and retrovirus restriction efficiency<\/a><\/h3>\n

Virology<\/em>, Volume 483, September 2015, Pages 141-148
\nKasandra B\u00e9langer, Marc-Andr\u00e9 Langlois<\/h4>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

RNA-binding residues in the N-terminus of APOBEC3G influence its DNA sequence specificity and retrovirus restriction efficiency Read the full article on ScienceDirect   APOBEC3 (A3) proteins are expressed in the cells of placental mammals. They have an important role in providing an effective innate immune defense against retroviral infection and zoonosis. Their claim to fame Read More…<\/a><\/p>\n","protected":false},"author":1,"featured_media":615,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5,632],"tags":[],"class_list":["post-609","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-highlighted-article","category-immunity-to-viruses"],"_links":{"self":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/609","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/comments?post=609"}],"version-history":[{"count":6,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/609\/revisions"}],"predecessor-version":[{"id":652,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/609\/revisions\/652"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/media\/615"}],"wp:attachment":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/media?parent=609"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/categories?post=609"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/tags?post=609"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}