Lysine residue at position 22 of the AID protein regulates its class switch activity.
<h4>Background</h4>Activation induced deaminase (AID) mediates class switch recombination and somatic hypermutation of immunoglobulin (Ig) genes in germinal centre B cells. In order to regulate its specific activity and as a means to keep off-target mutations low, several mechanisms have...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0030667&type=printable |
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| author | Roland Geisberger Michael Huemer Franz J Gassner Nadja Zaborsky Alexander Egle Richard Greil |
| author_facet | Roland Geisberger Michael Huemer Franz J Gassner Nadja Zaborsky Alexander Egle Richard Greil |
| author_sort | Roland Geisberger |
| collection | DOAJ |
| description | <h4>Background</h4>Activation induced deaminase (AID) mediates class switch recombination and somatic hypermutation of immunoglobulin (Ig) genes in germinal centre B cells. In order to regulate its specific activity and as a means to keep off-target mutations low, several mechanisms have evolved, including binding to specific cofactors, phosphorylation and destabilization of nuclear AID protein. Although ubiquitination at lysine residues of AID is recognized as an essential step in initiating degradation of nuclear AID, any functional relevance of lysine modifications has remained elusive.<h4>Methodology/principal findings</h4>Here, we report functional implications of lysine modifications of the human AID protein by generating a panel of lysine to arginine mutants of AID and assessment of their catalytic class switch activity. We found that only mutation of Lys22 to Arg resulted in a significant reduction of class switching to IgG1 in transfected primary mouse B cells. This decrease in activity was neither reflected in reduced hypermutation of Ig genes in AID-mutant transfected DT40 B cell lines nor recapitulated in bacterial deamination assays, pointing to involvement of post-translational modification of Lys22 for AID activity in B cells.<h4>Conclusions/significance</h4>Our results imply that lysine modification may represent a novel level of AID regulation and that Lys22 is important for effective AID activity. |
| format | Article |
| id | doaj-art-533339129a9440998e388d3f4e33ace4 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-533339129a9440998e388d3f4e33ace42025-08-20T02:30:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3066710.1371/journal.pone.0030667Lysine residue at position 22 of the AID protein regulates its class switch activity.Roland GeisbergerMichael HuemerFranz J GassnerNadja ZaborskyAlexander EgleRichard Greil<h4>Background</h4>Activation induced deaminase (AID) mediates class switch recombination and somatic hypermutation of immunoglobulin (Ig) genes in germinal centre B cells. In order to regulate its specific activity and as a means to keep off-target mutations low, several mechanisms have evolved, including binding to specific cofactors, phosphorylation and destabilization of nuclear AID protein. Although ubiquitination at lysine residues of AID is recognized as an essential step in initiating degradation of nuclear AID, any functional relevance of lysine modifications has remained elusive.<h4>Methodology/principal findings</h4>Here, we report functional implications of lysine modifications of the human AID protein by generating a panel of lysine to arginine mutants of AID and assessment of their catalytic class switch activity. We found that only mutation of Lys22 to Arg resulted in a significant reduction of class switching to IgG1 in transfected primary mouse B cells. This decrease in activity was neither reflected in reduced hypermutation of Ig genes in AID-mutant transfected DT40 B cell lines nor recapitulated in bacterial deamination assays, pointing to involvement of post-translational modification of Lys22 for AID activity in B cells.<h4>Conclusions/significance</h4>Our results imply that lysine modification may represent a novel level of AID regulation and that Lys22 is important for effective AID activity.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0030667&type=printable |
| spellingShingle | Roland Geisberger Michael Huemer Franz J Gassner Nadja Zaborsky Alexander Egle Richard Greil Lysine residue at position 22 of the AID protein regulates its class switch activity. PLoS ONE |
| title | Lysine residue at position 22 of the AID protein regulates its class switch activity. |
| title_full | Lysine residue at position 22 of the AID protein regulates its class switch activity. |
| title_fullStr | Lysine residue at position 22 of the AID protein regulates its class switch activity. |
| title_full_unstemmed | Lysine residue at position 22 of the AID protein regulates its class switch activity. |
| title_short | Lysine residue at position 22 of the AID protein regulates its class switch activity. |
| title_sort | lysine residue at position 22 of the aid protein regulates its class switch activity |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0030667&type=printable |
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