| Structural phylogenetic analysis of activation-induced deaminase function. | |
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MedLine Citation:
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PMID: 16785531 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In mammals, activation-induced deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) of Ig genes. SHM and CSR activities require separate regions within AID. A chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES) at the AID C terminus is necessary for CSR, and has been suggested to associate with CSR-specific cofactors. CSR appeared late in AID evolution, during the emergence of land vertebrates from bony fish, which only display SHM. Here, we show that AID from African clawed frog (Xenopus laevis), but not pufferfish (Takifugu rubripes), can induce CSR in AID-deficient mouse B cells, although both are catalytically active in bacteria and mammalian cell systems, albeit at decreased level. Like mammalian AID, Takifugu AID is actively exported from the cell nucleus by CRM1, and the Takifugu NES can substitute for the equivalent region in human AID, indicating that all the CSR-essential NES motif functions evolutionarily predated CSR activity. We also show that fusion of the Takifugu AID catalytic domain to the entire human noncatalytic domain restores activity in mammalian cells, suggesting that AID features mapping within the noncatalytic domain, but outside the NES, influence its function. |
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Authors:
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H Travis Ichikawa; Mark P Sowden; Andrew T Torelli; Jürgen Bachl; Pinwei Huang; Geoffrey S C Dance; Shauna H Marr; Jacques Robert; Joseph E Wedekind; Harold C Smith; Andrea Bottaro |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 177 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-20 Completed Date: 2006-08-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 355-61 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AY621657; AY621658 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Catalytic Domain / genetics Cell Line Cloning, Molecular Cytidine Deaminase / chemistry*, deficiency, genetics, physiology* Escherichia coli / enzymology, genetics Humans Immunoglobulin Class Switching / genetics Mice Molecular Sequence Data Mutation NIH 3T3 Cells Nuclear Export Signals / genetics Phylogeny* Recombinant Fusion Proteins / biosynthesis, genetics, physiology Sequence Homology, Amino Acid Takifugu Xenopus Proteins / chemistry, genetics, physiology Xenopus laevis |
| Grant Support | |
ID/Acronym/Agency:
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AI 059830/AI/NIAID NIH HHS; AI 45012/AI/NIAID NIH HHS; AI 54369 Z/AI/NIAID NIH HHS; CA 107355/CA/NCI NIH HHS; DK 43739/DK/NIDDK NIH HHS; GM 63162/GM/NIGMS NIH HHS; R25 GM 64133/GM/NIGMS NIH HHS; RR 15934/RR/NCRR NIH HHS; T32 HL 07152/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nuclear Export Signals; 0/Recombinant Fusion Proteins; 0/Xenopus Proteins; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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